WO2004112848A1

WO2004112848A1 - Lens care solutions for hydrogel contact lenses

Info

Publication number: WO2004112848A1
Application number: PCT/US2004/018377
Authority: WO
Inventors: Erning Xia; Joseph C. Salamone
Original assignee: Bausch & Lomb Incorporated
Priority date: 2003-06-16
Filing date: 2004-06-10
Publication date: 2004-12-29

Abstract

Contact lens cleaning and disinfecting compositions that reduce or eliminate wearer discomfort comprising a disinfecting amount of Alexidine. The solutions are effective in removing protein and lipid tear film deposits on both hard and soft contact lenses.

Description

LENS CARE SOLUTIONS FOR HYDROGEL CONTACT LENSES

Field of the Invention:

The present invention relates to the development of a gentle multipurpose solution for hydrogel contact lenses. More particularly, the present invention relates to a multi-purpose solution for hydrogel contact lenses that is a gentle, "one bottle" system with "no-rub" disinfecting and passive cleaning for both lipid and protein depositions.

Background of the Invention:

When contact lenses are removed from the eyes, they often retain on their surface a deposit or proteinaceous, oily and sebaceous matter that, if not removed, greatly reduces wettability properties and optical clarity of the lenses. In the case of hard contact lenses fabricated from poly(methyl methacrylate), the lenses are of such firmness that they can be treated using mechanical devices to remove deposits of contamination from their surfaces. Likewise, because hard contact lenses do not absorb appreciable amounts of water, the selection of cleaning agents is relatively non-critical. In many instances, use of even harsh disinfecting and cleaning agents on hard contact lenses does not create a problem. However, because of the hydrophilic properties of soft contact lenses formulated from materials such as poly(2-hydroxyethyl methacrylate), soft contact lenses do absorb more water than hard contact lenses. Consequently, greater care must be exercised in formulating cleansing solutions for soft contact lenses. With soft contact lenses, materials in the solutions can be absorbed and concentrated in the lenses which in-turn can damage the lens and even injure the eyes of the user.

In many instances, solutions intended for hard contact lenses are generally not adaptable for use with soft contact lenses. This may be illustrated, for instance, in the case of hard contact lens solutions containing benzalkonium chloride or chlorobutanol. If these hard contact lens solutions are used on soft contact lenses the solutions' important hydrophilic properties may be lost. Thus, in formulating contact lens care solutions, such as cleaning compositions, a number of factors need to be carefully weighed to assure total compatibility of the system in terms of functional efficaciousness, potential for damage to the lens and possible hazards to the wearer's eyes.

Multi-purpose solutions that clean and disinfect contact lenses have been described in the literature. For example, U.S. Patent Numbers 4,820,352 to Riedhammer et al. and 5,096,607 to Mowrey-McKee et al. disclose such solutions. More generally, contact lens solutions are disclosed in U.S. Patent Numbers 5,356,555 to Huth et al., 5,401 ,431 to Nakagawa et al., 5,409,546 to Nakagawa et al., 5,449,442 to Yamada et al., 5,487,788 to Kamiya et al., 5,505,953 to Chowhan, 5,556,480 to Rontome et al., 5,607,908 to Potini et al., 5,630,884 to Huth, 5,648,074 to Park et al., 5,654,262 to Desai et al., 5,800,807 to Huth et al., 5,820,696 to Kimura et al., 5,858,937 to Richard et al., 5,922,279 to Spooner, 6,024,954 to Park et al., and 6,121 ,327 to Tsuzuki et al.

Many multi-purpose contact lens solutions require the user to apply the solution to the contact lens and then to rub the contact lens, either between two fingertips or between a fingertip and the palm of the other hand. This step is known as "digital rubbing", and enhances cleaning. Where a multi-purpose solution is effective to clean and disinfect contact lenses without rubbing, maintaining contact lenses is simpler and easier. Thus, it is desirable to provide a safe and effective solution for cleaning contact lenses that does not require digital rubbing.

Disinfecting agents can cause wearer discomfort. Thus, it would be desirable to provide a safe and effective solution for cleaning soft contact lenses that reduces wearer discomfort while still maintaining efficacy as a disinfectant.

Summary of the Invention:

This invention provides a multi-purpose solution that requires no digital rubbing, i.e., "no-rub", for disinfecting and cleaning both lipid and protein deposits from a contact lens, and reduces or eliminates wearer discomfort. Solutions of the present invention may likewise be useful as in- eye conditioning solutions, in-eye cleaning solutions or in-eye cleaning and conditioning solutions for contact lens wearers. Solutions of the present invention may also be useful as in-eye drops, which condition the contact lens, and may also clean the contact lens. Such in-eye drops include antimicrobial agents for preservation of the solution, not for disinfection of a contact lens while being worn in an eye.

Loss of tight junctions and defects in the integrity of the corneal epithelium can be detected in some cases using a sodium fluorescein solution and visualizing the staining of the stroma by a slitlamp fluorometer. The composition of the present invention preferably comprises about 4.0 to about 5.0 ppm Alexidine. Alexidine has been associated with reduced or eliminated levels, of even non-clinically significant trace levels, of corneal and/or conjunctival staining, which is unexpected since other biguanides may cause such staining. The compositions of the present invention also exhibited greater comfort when compared with other no-rub multi-purpose solutions such as Opti-Free™ (Alcon Laboratories, Inc., Fort Worth, Texas), which contains Polyquaternium-1 as a disinfecting agent.

Brief Description of the Drawings:

FIGURE 1 is a graph of mean horizontal decentration vs. decentration for test and control solutions at insertion and 1-hour;

FIGURE 2 is a graph of mean movement vs. movement for test and control solutions at insertion and 1-hour; FIGURE 3 is a graph of mean inferior overlap vs. overlap for test and control solutions at insertion and 1-hour;

FIGURE 4 is a graph of mean comfort vs. analog comfort for test and control solutions at insertion and 1-hour;

FIGURE 5 is a graph of mean pre-lens tear film break-up time (TBUT) vs. break-up time (BUT) for test and control solutions at insertion and 1-hour;

FIGURE 6 is a graph of mean horizontal decentration vs. decentration for test and control solutions at insertion and 1-hour;

FIGURE 7 is a graph of mean movement vs. movement for test and control solutions at insertion and 1-hour;

FIGURE 8 is a graph of mean inferior overlap vs. overlap for test and control solutions at insertion and 1-hour;

FIGURE 9 is a graph of mean comfort vs. analog comfort for test and control solutions at insertion and 1-hour; and

FIGURE 10 is a graph of mean pre-lens tear film break-up time (TBUT) vs. break-up time (BUT) for test and control solutions at insertion and 1-hour.

Detailed Description of the Invention:

The present invention provides no-rub multi-purpose contact lens solutions for disinfecting and cleaning both lipid and protein deposits from a contact lens. The subject solutions provide greater lens comfort to the contact lens wearer. Compositions employed in this invention are aqueous solutions. Compositions of the present invention are preferably used as multi-purpose contact lens solutions to clean and disinfect soft-type contact lenses manufactured from hydrogel biomaterials such as for example but not limited to silicone hydrogel biomaterials. Silicone hydrogel contact lenses include for example but are not limited to contact lenses manufactured from siloxy- containing monomers, siloxy-containing macromolecular monomers, and copolymers with fluoro-containing monomers, alkyl-, cycloalkyl-, arylalkyl- and aryl-containing derivatives of acrylic or methacrylic acid, or itaconic acid, as well as styrenes, butudienes or isoprenes. Such systems could also be copolymerized with hydrophilic monomers such as 2-hydroxyethyl methacrylate, N-vinylpyrrolidone, N,N-dimethylacrylamide and (meth)acrylic acid.

Compositions of the present invention preferably include one or more polyethers. Polyethers employed in the subject compositions may include for example but are not limited to polyethers based upon poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), i.e., (PEO-PPO-PEO), or poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide), i.e., (PPO- PEO-PPO), or a combination thereof. PEO-PPO-PEO and PPO-PEO-PPO, such as for example poloxamers and poloxamines, are commercially available under the trade names Pluronics™, R-Pluronics™, Tetronics™ and R-Tetronics™ (BASF Wyandotte Corp., Wyandotte, Michigan). Polyethers in the subject ophthalmic solutions exhibit ready absorption into hydrogel biomaterials such as those used in the manufacture of soft-type contact lenses. Polyethers in the subject ophthalmic solutions, after absorption into hydrogel biomaterials to a high concentration, exhibit slow release from the hydrogel biomaterials over a period of time in an aqueous environment. In accordance with the present invention, the one or more polyethers release slowly from a worn contact lens into an eye's tear film over a long time period to produce longer lasting wetting performance, improved lubricity, improved end-of-the-day comfort and reduced feeling of dryness from wearing contact lenses.

Compositions of the present invention provide efficient performance at polyether surfactant concentrations ranging from as little as about 0.01 to about 15 weight percent by volume (w/v). Greater concentrations may be used, but provide no added benefit and only increase the potential for irritating eye tissues. More preferably, the solutions of the subject invention will contain from about 0.1 to about 5 weight percent polyether surfactant.

The subject compositions in addition to polyethers likewise include one or more, but at least one, cationic polyelectrolyte that functions to control lens swelling caused by the absorption of high concentrations of polyethers as disclosed in U.S. Patent Application Serial Number 10/392,743, incorporated herein in its entirety by reference. By controlling lens swelling, visual acuity is maintained. Suitable cationic polyelectrolytes include for example but are not limited to polyquaternium 1, polyquaternium 10, polyquatemium 11, polyquaternium 16, polyquaternium 44 and polyquaternium 46, but preferably polyquaternium 10 available under the trade name Polymer JR (BASF Wyandotte Corp.). Preferably, the ophthalmic solution of the present invention comprises about 0.001 to about 5 weight percent by volume and more preferably from about 0.01 to about 0.5 weight percent of one or more cationic polyelectrolytes for control of lens swelling.

To provide for both cleaning and disinfection of a contact lens in a single step, compositions of the present invention contain an antimicrobial agent. The use of Alexidine in formulations of the present invention is associated with reduced levels of corneal and/or conjunctival staining. It is unexpected that Alexidine would be associated with reduced or eliminated levels of corneal and/or conjunctival staining since other biguanides may cause such staining. Accordingly, Alexidine, its salts, non-polymeric, non- chloro-containing bis(biguanide)s, or combinations thereof, are the preferred antimicrobial agents, with Alexidine-2HCI being the most preferred. Preferably, the antimicrobial agent will be used in a disinfecting amount or an amount from about 0.0001 to about 0.5 weight percent by volume.

A disinfecting amount of an antimicrobial agent is an amount that will at least partially reduce the microorganism population in the formulations employed. Preferably, a disinfecting amount is that which will reduce the microbial burden by two log orders in four hours and more preferably by one log order in one hour. Most preferably, a disinfecting amount is an amount which will eliminate the microbial burden on a contact lens when used in the regimen for the recommended soaking time as established by ISO (International Standards for Ophthalmic Optics)/FDA Stand-Alone Procedures for Disinfection Test (ISO/DIS 14729; 2001). Typically, such agents are present in concentrations ranging from about 0.00001 to about 0.5 weight percent based on volume (w/v), and more preferably, from about 0.00003 to about 0.05% weight percent.

Compositions of the present invention also include one or more but at least one osmolality agent in a concentration sufficient to increase the cleaning efficacy of the solution without adversely affecting the antimicrobial efficacy of the solution. Suitable osmolality agents include for example but are not limited to metal halides such as magnesium, calcium, sodium and potassium chloride, diols and polyols such as propylene glycol and glycerin, mono-, di-, or polysaccharides (saccharides), such as dextrose and trehalose, as well as amino acids such as lysine. Such osmolality agents may be used individually or in combinations in amounts ranging from about 0.01 to about 2.5 weight percent by volume (w/v) and preferably so that the final osmotic value of the solution has an osmolality of more than 200 mOsm/kg, and preferably from 220 to 400 mOsm/kg, and more preferably from 220 to 320 mOsm/kg.

In order to maintain the pH of the solutions within the range of about 6.5 to 7.8, one or more suitable buffers may be added to the subject compositions. Examples of useful buffering agents include for example, but are not limited to alkali metal salts such as potassium or sodium carbonates, acetates, borates, phosphates, and citrates, and weak acids such as acetic and boric acids. Preferred buffering agents include boric acid, sodium borate, potassium citrate, citric acid, sodium bicarbonate, including combinations of Na₂PO₄, NaH₂PO and KH₂PO , and aminoalcohols. Generally, buffers will be used in amounts ranging from about 0.01 to about 2.5, and preferably, from about 0.1 to about 1.5 percent by weight/volume (w/v).

Compositions of the present invention are described in still greater detail in the examples provided below. However, it is to be understood that the following examples are for illustrative purposes only and do not purport to be wholly definitive as to conditions and scope of the present invention.

EXAMPLE 1 - Clinical Performance Study:

A test solution, i.e., Solution 1 , was prepared as set forth below in Table 1 and compared against that of ReNu™ MultiPlus No Rub Formula Multi-Purpose Solution (Bausch & Lomb, Incorporated), hereinafter, "ReNu MultiPlus", in a clinical performance study.

TABLE 1

Test Solutions

Inqredients ReNu MultiPlus (% W/W) Solution 1 (% W/W)

Pluronic F127 0 2.00

Tetronic 1107 1.00 1.00

Sodium Chloride 0.49 0.09

Boric Acid 0.64 0.85

Sodium Borate 0.09 0

EDTA 0.11 0

Sodium Phosphate (monobasic) 0 0.15

Sodium Phosphate (dibasic) 0 0.31

Polymer JR 0 0.02

PHMB HCI 1.1 ppm 0

Alexidine 2HCI 0 4.5 ppm

Dequest 2016 0.10 0.10

Purified Water Q.S. to lOO gm Q.S. to

100 gm

EDTA = Ethylenediaminetetraacetic acid PHMB HCI = poly(hexamethylene biguanide) Dequest™ 2016 (Solutia Inc., St. Louis, Missouri) The objective of this study was to assess the short-term (1-hour) clinical performance of Solution 1 as compared to ReNu MultiPlus when used with PureVision™ lenses (Bausch & Lomb, Incorporated). To this end, twenty-four (24) subjects, all habitual soft spherical contact lens wearers, were enrolled in the study. The test solution, Solution 1 , was prepared in accordance with the present invention. The control solution, ReNu MultiPlus, was taken from inventory (lot # GL2029). The lenses used in this study were standard PureVision lenses taken from inventory.

Each well of each of the Bausch & Lomb lens cases was pre-treated using a single, 4-hour minimum soak, with either Solution 1 or ReNu MultiPlus. For each case, the well treated with Solution 1 was randomly determined and the fellow well received ReNu MultiPlus. All PureVision lenses were pre-treated using two separate, 4-hour minimum soaks, with either Solution 1 or ReNu MultiPlus, in the pre-treated lens cases, following the same randomization used for the lens case wells.

Each subject was fitted with a pre-treated lens pair. Each lens was evaluated for centration, movement, comfort, wetting, deposits and pre-lens tear film break-up time. Each subject wore a Solution 1 /PureVision lens and a ReNu MultiPlus/PureVision lens on contralateral eyes for approximately 1 hour. The eyes receiving Solution 1 /PureVision lenses were randomly assigned. Subjects and the investigator were masked to solution identity. Testing was repeated after 1 hour of lens wear. Unless otherwise noted, a 2-way repeated measures ANOVA incorporating the factors Time (insertion and 1-hour) and Solution (Solution 1 - test vs. ReNu MultiPlus - control) was used to test for differences in means for each of the parametric dependent variables. The data for each of the ordinal dependent measures, i.e., those assigned a clinical grade, were analyzed using the Wilcoxon Matched Pairs procedure. Differences at the alpha = 0.05 level were considered to be statistically significant.

There was a statistically significant difference in mean horizontal decentration with respect to the Time x Solution effect (ANOVA, p<0.005): lenses pre-treated with test solution had a slight decrease in decentration while those pre-treated with control solution had a slight increase in decentration. There were no significant differences noted with respect to the Time and Solution effects (ANOVA, p>0.89 in both cases) as illustrated in Figure 1.

There was a statistically significant difference in mean movement with respect to the Time effect (ANOVA, p<0.003): all lenses, both those pre- treated with test and pre-treated with control solutions, exhibited less movement at 1-hour than at insertion. There were no significant differences noted with respect to the Solution and Time x Solution effects (ANOVA, p>0.77 in both cases) as illustrated in Figure 2.

There was a statistically significant difference in mean inferior overlap with respect to the Time and Solution effects (ANOVA, p<0.004 in both cases): all lenses, both those pre-treated with test and pre-treated with control solutions, exhibited less inferior overlap at 1-hour than at insertion. The lenses pre-treated with Solution 1 exhibited less inferior overlap when compared to lenses pre-treated with ReNu MultiPlus. There was no significant difference noted with respect to the Time x Solution effect (ANOVA, p>0.75) as illustrated in Figure 3.

There was no statistically significant difference in mean comfort with respect to the Time, Solution, and Time x Solution effects (ANOVA, p>0.09 in all cases) as illustrated in Figure 4.

There was a statistically significant difference in mean break-up time with respect to the Time effect (ANOVA, p<0.01): all lenses, both those pre- treated with Solution 1 and pre-treated with ReNu MultiPlus, exhibited less , break-up time at 1-hour than at insertion. There were no significant differences noted with respect to the Solution and Time x Solution effects (ANOVA, p>0.10 in both cases) as illustrated in Figure 5.

There was no statistically significant difference between the test and control solutions for lens surface wettability (Wilcoxon Matched Pairs, p>0.90 in all cases).

There was no statistically significant difference between the test and control solutions for lens surface deposition (Wilcoxon Matched Pairs, p>0.18 in all cases).

In summary, twenty-four subjects were enrolled in a 1-hour, non- dispensing evaluation comparing Solution 1 (test solution) to ReNu MultiPlus (control solution) using PureVision lenses. The test solution exhibited statistically significant less lens inferior overlap when compared to the control solution. There were no statistically significant differences noted between the solutions with respect to lens horizontal decentration, lens movement, comfort, pre-lens tear film break-up time, lens wettability and lens deposition. All study results are set forth below in Table 2.

TABLE 2

Study of Solution 1 Compared to ReNu MultiPlus Using PureVision Lenses

Summary of Results

Insertion Valid N Mean Minimum Maximum Std.

Dev.

Movement Tl 24 0.51 0.20 1.40 0.30

Movement CI 24 0.51 0.20 1.40 0.26

Inferior overlap Tl 24 1.75 1.20 2.60 0.33

Inferior overlap CI 24 1.85 1.20 2.60 0.34

Decentration Tl 24 0.23 0.00 0.60 0.15

Decentration CI 24 0.17 0.00 0.50 0.12

Analog comfort Tl 24 93.96 76.00 99.00 6.08

Analog comfort CI 24 93.08 75.00 99.00 6.78

TBUT Tl 24 11.50 6.00 28.00 5.36

TBUT CI 24 13.50 6.00 29.00 6.38

Wettability Tl 24 0.00 0.00 0.00 0.00

Wettability CI 24 0.00 0.00 0.00 0.00

Deposition Tl 24 0.04 0.00 1.00 0.20

Deposition CI 24 0.08 0.00 1.00 0.28 TABLE 2 - Continued

Insertion Valid N Mean Minimum Maximum Std.

Dev.

1-Hour

Movement Tl 24 0.41 0.10 1.40 0.30

Movement CI 24 0.39 0.10 0.80 0.20

Inferior overlap Tl 24 1.67 1.00 2.20 0.33

Inferior overlap CI 24 1.75 1.20 2.40 0.35

Decentration Tl 24 0.18 0.00 0.40 0.12

Decentration CI 24 0.22 0.00 0.60 0.16

Analog comfort Tl 24 94.96 80.00 99.00 6.06

Analog comfort CI 24 94.83 81.00 99.00 6.08

TBUT TI 24 10.17 5.00 19.00 3.45

TBUT CI 24 10.29 6.00 23.00 4.63

Wettability Tl 24 0.13 0.00 1.00 0.34

Wettability CI 24 0.13 0.00 1.00 0.34

Deposition Tl 24 0.04 0.00 1.00 0.20

Deposition CI 24 0.21 0.00 2.00 0.51

Tl = Test Solution 1/PureVision lenses

CI = Control ReNu MultiPlus/PureVision lenses EXAMPLE 2 - Clinical Performance Study:

A test solution, i.e., Solution 1 , was prepared as set forth above in Table 1 and compared against that of Opti-Free Express™ No Rub Multipurpose Disinfecting Solution (Alcon Laboratories, Incorporated), hereinafter, "Opti-Free", in a clinical performance study.

The objective of this study was to assess the short-term (1-hour) clinical performance of Solution 1 as compared to Opti-Free when used with PureVision™ lenses (Bausch & Lomb, Incorporated). To this end, twenty- four (24) subjects, all habitual soft spherical contact lens wearers, were enrolled in the study. The test solution, Solution 1, was prepared in accordance with the present invention. The control solution, Opti-Free, was taken from inventory (lot # 33813F). The lenses used in this study were standard PureVision lenses taken from inventory.

Each well of the Bausch & Lomb lens cases was pre-treated using a single, 4-hour minimum soak, with either Solution 1 or Opti-Free. For each case, the well treated with Solution 1 was randomly determined and the fellow well received Opti-Free. All PureVision lenses were pre-treated using two separate, 4-hour minimum soaks, with either Solution 1 or Opti-Free, in the pre-treated lens cases, following the same randomization used for the lens case wells.

Each subject was fitted with a pre-treated lens pair. Each lens was evaluated for centration, movement, comfort, wetting, deposits and pre-lens tear film break-up time. Each subject wore a Solution 1 /PureVision lens and a Opti-Free /PureVision lens on contralateral eyes for approximately 1 hour. The eyes receiving Solution 1/PureVision lenses were randomly assigned. Subjects and the investigator were masked to solution identity. Testing was repeated after 1 hour of lens wear.

Unless otherwise noted, a 2-way repeated measures ANOVA incorporating the factors Time (insertion and 1-hour) and Solution (Solution 1 - test vs. Opti-Free - control) was used to test for differences in means for each of the parametric dependent variables. The data for each of the ordinal dependent measures, i.e., those assigned a clinical grade, were analyzed using the Wilcoxon Matched Pairs procedure. Differences at the alpha = 0.05 level were considered to be statistically significant.

There was a statistically significant difference in mean horizontal decentration with respect to the Time effect (ANOVA, p<0.03): all lenses, both those pre-treated with test and pre-treated with control solutions, exhibited greater decentration at 1-hour than at insertion as illustrated in Figure 6. No significant differences were noted between test and control solutions.

There was a statistically significant difference in mean movement with respect to the Time and Solution effects (ANOVA, p<0.008 in both cases). All lenses, both those pre-treated with test solution and pre-treated with control solution, exhibited less movement at 1-hour than at insertion. The lenses pre-treated with test solution exhibited less movement when compared to lenses pre-treated with control solution as illustrated in Figure 7. Mean lens movement was 0.40 mm and 0.48 mm for test and control solutions, respectively.

There was a marginally statistically significant difference in mean inferior overlap with respect to the Time effect (ANOVA, p<0.06): all lenses, both those pre-treated with test and pre-treated with control solutions, exhibited less inferior overlap at 1-hour than at insertion. No significant differences were noted between test and control solutions as illustrated in Figure 8.

There was a statistically significant difference in mean comfort with respect to the Solution effect (ANOVA, p<0.05). The test solution exhibited greater comfort when compared to the control solution. Mean comfort was 94.94 and 93.06 for test and control solutions, respectively, as illustrated in Figure 9.

There was no statistically significant difference in mean break-up time with respect to the Time, Solution, and Time x Solution effects (ANOVA, p>0.09 in all cases) as illustrated in Figure 10.

There was no statistically significant difference between the test and control solutions for lens surface wettability (Wilcoxon Matched Pairs, p>0.11 in all cases).

There was no statistically significant difference between the test and control solutions for lens surface deposition (Wilcoxon Matched Pairs, p>0.59 in all cases).

In summary, twenty-four subjects were enrolled in a 1-hour, non- dispensing evaluation comparing Solution 1 (test solution) to Opti-Free (control solution) using PureVision lenses. The test solution exhibited statistically significant less lens movement and greater comfort when compared to the control solution. There were no statistically significant differences noted between the test and control solutions with respect to lens centration, pre-lens tear film break-up time, lens wettability and lens deposition. All study results are set forth below in Table 3.

TABLE 3

Study of Solution 1 Compared to Opti-Free Using PureVision Lenses

Summary of Results

Insertion Valid N Mean Minimum Maximum Std.

Dev.

Movement Tl 24 0.47 0.20 1.20 0.26

Movement CI 24 0.54 0.20 1.20 0.24

Inferior overlap Tl 24 1.75 0.80 2.60 0.40

Inferior overlap CI 24 1.82 1.00 2.80 0.42

Decentration Tl 24 0.14 0.00 0.30 0.09

Decentration CI 24 0.20 0.00 0.45 0.13

Analog comfort Tl 24 95.42 68.00 99.00 7.88

Analog comfort CI 24 93.13 68.00 100.00 9.68

TBUT Tl 24 11.54 6.00 21.00 4.29

TBUT CI 24 10.92 7.00 19.00 2.87

Wettability Tl 24 0.00 0.00 0.00 0.00

Wettability CI 24 0.00 0.00 0.00 0.00

Deposition Tl 24 0.04 0.00 1.00 0.20

Deposition CI 24 0.08 0.00 2.00 0.41 TABLE 3 - Continued

Insertion Valid N Mean Minimum Maximum Std.

Dev.

1-Hour

Movement Tl 24 0.38 0.10 1.20 0.24

Movement CI 24 0.41 0.10 1.20 0.25

Inferior overlap Tl 24 1.65 0.80 2.60 0.42

Inferior overlap CI 24 1.71 1.00 2.60 0.40

Decentration Tl 24 0.19 0.00 0.35 0.12

Decentration CI 24 0.21 0.00 0.45 0.12

Analog comfort Tl 24 94.46 70.00 99.00 7.52

Analog comfort CI 24 93.00 60.00 100.00 10.57

TBUT TI 24 10.58 5.00 19.00 3.86

TBUT CI 24 9.42 3.00 24.00 4.64

Wettability Tl 24 0.00 0.00 0.00 0.00

Wettability CI 24 0.13 0.00 1.00 0.34

Deposition Tl 24 0.13 0.00 1.00 0.34

Deposition CI 24 0.08 0.00 1.00 0.28

Tl = Test Solution 1/PureVision lenses CI = Control Opti-Free/PureVision lenses The compositions of the present invention may be effectively used as multi-purpose no-rub contact lens solutions for removing and dispersing protein and lipid tear film deposits on both hard and soft-type contact lenses. For example, the subject compositions may be used when the wearer of contact lenses removes the contact lenses from the eyes. The contact lenses may be soaked in solutions of the present compositions at room temperature for a period ranging from about four to twelve hours. The lenses are then removed from the solution and replaced on the eyes. The wearer may optionally rinse the lenses in a preserved saline solution before replacing the lenses on the eyes.

When the cleaning process includes a rinsing step, however, the cleaning solution may contain higher concentrations of surfactant, e.g., 3 to 15 weight percent. However, the rinsing step may be omitted when, for example, the cleaning solution contains up to 1.5 weight percent of surfactant. In addition to the soaking method, the solutions disclosed herein are adaptable for use in equipment such as ultrasonic cleaners. Furthermore, because the solutions are also stable when heated to temperatures in the range of 80° to 90°C, they are also adaptable for use with high temperature disinfecting methods. Typically, lenses are heated to 80° C in a disinfecting unit containing the solution for a time period of at least 10 minutes, removed and rinsed with isotonic saline. While there is shown and described herein compositions for ophthalmic solutions, and methods of making and using the same, it will be manifest to those skilled in the art that various modifications may be made without departing from the spirit and scope of the underlying inventive concept. The present invention is likewise not intended to be limited to particular ophthalmic solutions or methods described herein except insofar as indicated by the scope of the appended claims.

Claims

We claim:

1. A composition comprising: one or more polyethers; one or more cationic polyelectrolytes; one or more osmolality agents; and a disinfecting amount of Alexidine, its salts, or a combination thereof.

2. A no-rub contact lens cleaning and disinfecting solution comprising: one or more polyethers; one or more cationic polyelectrolytes; one or more osmolality agents; and a disinfecting amount of Alexidine, its salts, or a combination thereof.

3. A no-rub contact lens cleaning and disinfecting solution that reduces or eliminates corneal or conjunctival staining comprising: one or more polyethers to improve comfort of said contact lens for said contact lens wearer; one or more cationic polyelectrolytes to control contact lens swelling; one or more osmolality agents to improve in-eye solution comfort; and a disinfecting amount of Alexidine, its salts, or a combination thereof.

4. A no-rub contact lens cleaning and disinfecting solution that reduces or eliminates wearer discomfort comprising: one or more polyethers; one or more cationic polyelectrolytes; one or more osmolality agents; and a disinfecting amount of Alexidine, its salts, or a combination thereof.

5. The composition of claim 1 wherein said one or more polyethers are selected from the group consisting of poloxamers, poloxamines and combinations thereof.

6. The composition of claim 1 wherein said one or more polyethers are present in an amount within the range of about 0.01 to about 15 weight percent.

7. The composition of claim 1 wherein said one or more cationic polyelectrolytes are selected from the group consisting of polyquaternium 1 , polyquaternium 10, polyquaternium 11 , polyquaternium 16, polyquaternium 44, polyquaternium 46 and combinations thereof.

8. The composition of claim 1 wherein said one or more cationic polyelectrolytes are present in an amount within the range of about 0.001 to about 5 weight percent.

9. The composition of claim 1 wherein said disinfecting amount is of Alexidine.

10. The composition of claim 1 wherein said disinfecting amount is of Alexidine, its salts or a combination thereof present in an amount within the range of about 0.00001 to about 0.5 weight percent and reduces or eliminates corneal staining.

11. The composition of claim 1 wherein said one or more osmolality agents are selected from the group consisting of metal halides, diols, polyols, saccharides, amino acids and combinations thereof.

12. The composition of claim 1 wherein said one or more osmolality agents are present in an amount within the range of about 0.01 to about 2.5 weight percent.

13. The composition of claim 1 wherein said one or more osmolality agents are present in a concentration sufficient to increase cleaning efficacy without adversely affecting antimicrobial efficacy.

14. The composition of claim 1 wherein said composition includes one or more buffering agents.

15. The composition of claim 1 wherein said composition includes one or more buffering agents in an amount effective in maintaining the pH of the composition within the range of about 6.5 to about 7.8.

16. The composition of claim 1 wherein said one or more buffering agents are present in an amount within the range of about 0.01 to about 2.5 weight percent.

17. A method of making the composition of claim 1 comprising: combining one or more polyethers; one or more cationic polyelectrolytes; one or more osmolality agents; and a disinfecting amount of Alexidine, its salts or a combination thereof.

18. A method of using the composition of claim 1 comprising: soaking a contact lens in said composition for a period of time of about 4 to about 12 hours.

19. The solution of claim 2, 3 or 4 wherein said one or more polyethers are selected from the group consisting of poloxamers, poloxamines and combinations thereof.

20. The solution of claim 2, 3 or 4 wherein said one or more polyethers are present in an amount within the range of about 0.01 to about 15 weight percent.

21. The solution of claim 2, 3 or 4 wherein said one or more cationic polyelectrolytes are selected from the group consisting of polyquaternium 1 , polyquaternium 10, polyquaternium 11 , polyquaternium 16, polyquaternium 44, polyquaternium 46 arid combinations thereof.

22. The solution of claim 2, 3 or 4 wherein said one or more cationic polyelectrolytes are present in an amount within the range of about 0.001 to about 5 weight percent.

23. The solution of claim 2, 3 or 4 wherein said disinfecting amount is of Alexidine.

24. The solution of claim 2, 3 or 4 wherein said disinfecting amount is of Alexidine, its salts or a combination thereof present in an amount within the range of about 0.00001 to about 0.5 weight percent with reduced or eliminated levels of corneal staining.

25. The solution of claim 2, 3 or 4 wherein said one or more osmolality agents are selected from the group consisting of metal halides, diols, polyols, saccharides, amino acids and combinations thereof.

26. The solution of claim 2, 3 or 4 wherein said one or more osmolality agents are present in an amount within the range of about 0.01 to about 2.5 weight percent.

27. The solution of claim 2, 3 or 4 wherein said one or more osmolality agents are present in a concentration sufficient to increase cleaning efficacy without adversely affecting antimicrobial activity.

28. The solution of claim 2, 3 or 4 wherein said composition includes one or more buffering agents.

29. The solution of claim 2, 3 or 4 wherein said composition includes one or more buffering agents in an amount effective in maintaining the pH of the solution within the range of about 6.5 to about 7.8.

30. The solution of claim 2, 3 or 4 wherein said one or more buffering agents are present in an amount within the range of about 0.01 to about 2.5 weight percent.

31. A method of making the solution of claim 2, 3 or 4 comprising: combining one or more polyethers; one or more cationic polyelectrolytes; one or more osmolality agents; and a disinfecting amount of Alexidine, its salts or a combination thereof.

32. A method of using the solution of claim 2, 3 or 4 comprising: soaking a contact lens in said composition for a period of time of about 4 to about 12 hours.

33. The composition of claim 1 wherein said composition is useful as an in-eye conditioning solution, an in-eye cleaning solution or an in-eye cleaning and conditioning solution.

34. The composition of claim 1 wherein said composition is useful as in-eye drops to condition a contact lens while worn in an eye.

35. The composition of claim 1 wherein said composition is useful as in-eye drops to condition and clean a contact lens while worn in an eye.

36. A composition comprising: one or more polyethers; one or more cationic polyelectrolytes; one or more osmolality agents; and a disinfecting amount of Alexidine or its salts.

37. The composition of claim 36 wherein said one or more polyethers are Tetronic 1107 and Pluronic F127.

38. The composition of claim 36 wherein said one or more cationic polyelectrolytes are polyquaternium 10.

39. The composition of claim 36 wherein said one or more osmolality agents are sodium chloride.

40. A composition comprising: Tetronic 1107 and Pluronic F127; polyquaternium 10; sodium chloride; and a disinfecting amount of Alexidine , its salts or a combination thereof.