WO2001023509A1

WO2001023509A1 - Composition and method for treating contact lenses

Info

Publication number: WO2001023509A1
Application number: PCT/US2000/027058
Authority: WO
Inventors: Edward J. Ellis; Jeanne Y. Ellis
Original assignee: Vista Scientific Llc
Priority date: 1999-09-30
Filing date: 2000-09-29
Publication date: 2001-04-05

Abstract

The present invention discloses an efficacious, non-irritating surfactant for the cleaning of contact lenses, particularly rigid gas permeable and silicone hydrogel lenses which have been shown to accumulate lipid deposits. These lipid deposits are very tenacious and difficult to remove with most conventional contact lens cleaners. Cleaning formulations containing methyl glucose sesquistearate have been found to effectively remove lipid deposits from contact lenses in a passive manner. For this reason methyl glucose sesquistearate finds particular utility as the active ingredient in multipurpose contact lens solutions.

Description

COMPOSITION AND METHOD FOR TREATING CONTACT LENSES

FIELD OF THE INVENTION:

The present invention relates to ophthalmic solutions and more particularly to a composition for use with contact lenses and a method of treating the same.

BACKGROUND OF THE INVENTION: Contact lenses are subjected to the ocular environment for long periods of time each day. As a result of being in contact with the tear film and ocular debris, lenses have a tendency to build up surface deposits. The deposit may be formed from endogenous materials, such as proteins, lipids and mucins, but also may be the result of exogenous materials, such as cosmetic ingredients. To ensure comfortable wear and good vision, these surface deposits must be removed periodically, usually once a day for rigid gas permeable lenses and daily wear soft hydrogel lenses. For flexible wear lenses the cleaning may be less frequent.

Contact lens cleaners can be classified into two categories, primary, or "daily cleaners" and secondary, or "adjunct" cleaners. The daily cleaners are surfactant based and are formulated to target the soils most commonly found on either soft hydrogel lenses or rigid lenses. The adjunct cleaners are generally enzyme based and target proteinaceous matter. These enzyme cleaners are usually recommended for weekly use with soft hydrogel lenses. However, more recently, enzyme treatment of rigid lenses has been gaining favor. The contact lens cleaners on the market today contain a surfactant and/or combination of surfactants, selected from the non ionic, anionic or amphoteric categories. The use of a cationic surfactant in a contact lens cleaner is rare. Abrasives, or particulate matter in contact lens cleaners has been taught to assist the surfactant(s) in removal of soils. There have been reports in the contact lens industry that cleaners with harsh abrasives will change the power of rigid lenses over time due to a "polishing" effect.

The cleaning process for contact lenses can be either active, digital rubbing of the lens surface, or passive, soaking the lens in the cleaning solution. These cleaning processes may be combined, that is, the contact lens is removed from the eye, digitally rubbed with the cleaning solution, then placed in that same cleaning solution overnight to allow passive cleaning to occur. Examples of this regimen for rigid lens would be the Boston Simplicity® solution and the Menicon Claris® system. For soft hydrogel lenses there are a number of products available that are considered multipurpose solutions, that is, cleaning, soaking and disinfection. Examples include Bausch & Lomb Renu®, Alcon Optifree®, Ciba Solocare® and Allergan Complete®. The surfactant(s) in contact lens cleaners serves a dual role. One role is to

"solubilize" the soil on the lens into micelles. The other role is to "displace" the soil from the lens surface. This is accomplished by breaking the hydrophobic interaction between the soil and the lens surface, leading to a more thermodynamically preferred state. The use of abrasives help "displace" soils from the surface, thus aiding the surfactant(s).

Surfactant based contact lens cleaners on the market today vary in performance depending on the surfactant system chosen and the regimen recommended. For instance, surfactant/abrasive cleaners that are rinsed from the lens perform reasonably well, while multipurpose solution cleaners tend to be less effective due to the requirement that the cleaner be non irritating to the eye. Because soft hydrogel lenses have a rather porous structure, surfactants will tend to be absorbed into the lens structure, only to be released later into the ocular environment during lens wear.

Given the many types of contact lenses available today, i.e. low to high oxygen permeable rigid lenses, conventional and disposable hydrogel lens of various water contents and surface charges, and the new soft silicone hydrogel lenses, there is a need for improved cleaning products and processes. The trend is toward more efficacious and convenient cleaning products, especially one bottle systems, that provide a margin of safety when used by the patient.

SUMMARY OF THE INVENTION:

The present invention includes methods for treating contact lenses and compositions for the same. This invention includes contacting a lens with an aqueous solution comprising a methyl glucose sesquistearate represented by the following formula:

o

O — (CC₁₇H₃₅)₀._{5 )} (H)_0>5

O

wherein x + y = 15 to 25. The compound of the present invention may further comprise buffers and antimicrobial agents. The compositions of this invention may be in the form of a stand alone cleaner to be used in combination with a wetting, soaking and disinfecting solution. Alternatively, the present invention may be in the form of a one step solution that provides simultaneous cleaning, wetting and disinfecting of contact lenses. In one preferred embodiment the present compositions provide a one step cleaning, wetting and disinfecting regimen for rigid gas permeable lenses. In another preferred embodiment the present compositions are utilized as one step cleaning and disinfecting solutions for conventional hydrogel lenses and soft, gas permeable silicone (including both hydrogel and non hydrogel) lenses. As such, the present invention offers distinct and significant advantages over known cleaning and disinfecting regimens for contact lenses.

DETAILED DESCRIPTION OF THE INVENTION:

It is an object of this invention to provide improved cleaning preparations for contact lenses. It is a further objective to provide cleaning preparations that are effective in removing lipids and other hydrophobic debris from the lens surface simply by soaking the lens in the solution for a period of time. This invention can be used with all contact lenses, such as conventional hydrophilic soft lenses, rigid gas permeable lenses and silicone (including both hydrogel and non hydrogel) lenses. In a preferred embodiment this invention is employed with rigid gas permeable lenses. Such lenses are commonly prepared from monomers such as silicone acrylates and methacrylates, fluoroacrylates and methacrylates, methylmethacrylate, methacrylic acid and vinylpyrrolidone. The oxygen permeability of such lenses can range form about 12 to 150 or more in Dk units. The present invention includes an aqueous solution comprising a methyl glucose sesquistearate. One preferred methyl glucose sesquistearate is available from Amerchol Corp. as PEG-20 methyl glucose sesquistearate and is represented by the following formula:

O

O — (CC₁₇H₃₅)₀._{5 >} (H)o.₅

II

O wherein x + y = 15 to 25 and more preferably x+ y = about 20.

It should be appreciated that methyl glucose sesquistearate obtained from other manufacturers is suitable in the practice of this invention.

The use of certain methyl glucose derivatives in contact lens solutions is known. For example, U.S. Pat. No. 5,405,878 to Ellis et al. discloses a cationic glucoside, Glucquat® 125 from Amerchol Corp., as a wetting agent for contact lenses. Furthermore, in U.S. Patent No. 5,401,327 and 5,711,823 to Ellis et al an ethoxylated glucose derivative, Glucam® E-20 is disclosed as a wetting agent for contact lenses. The above mentioned Glucquat® 125 and Glucam® E-20 are not effective in moving lipid and lipid-like deposits from soiled contact lenses.

In a recently published European application, EPO 877 075 Al, to Soyer et al. a ethoxylated methyl glucose dioleate is disclosed as a component in a contact lens cleaning solution. However, within the scope of the present invention this material was not found effective at removing lipid deposits from contact lenses.

The present applicants have found that methyl glucose sesquistearate is a superior lipid cleaner that is not irritating to eye. In that context methyl glucose sesquistearate provides the basis for improved contact lens cleaners. The specific quantities of methyl glucose sesquistearate used in the present invention will vary depending on the application. Typical ranges are from about 0.001% by weight to about 0.30% by weight. The aqueous contact lens cleaning solutions of the present invention may also contain various other components including, but not limited to, buffering agents, tonicity adjusting agents, chelating and/or sequestering agents, viscosifiers, surfactants, humectants, and antimicrobial agents. Furthermore, the subject solutions preferably has a pH between 6.0 and 8.0. Any pharmaceutically acceptable buffer system may be utilized in the present invention and includes phosphates, borates, acetates and carbonates. Most preferred are the phosphate and borates at total levels of from about 0.1% by weight to about 1.5% by weight of the total composition.

Tonicity adjusting agents refer to those agents that are used to modify the osmolality of an ophthalmic formulation. Examples of suitable tonicity agents include, but are not limited to, sodium chloride, potassium chloride, mannitol, sorbitol, glycerin, propylene glycol and mixtures thereof. In one embodiment the tonicity agent is selected from inorganic salts and mixtures thereof.

The viscosity of the cleaning compositions may be adjusted by adding a viscosity builder. In practice, cleaning compositions for soft hydrogel contact lenses are generally in the viscosity range of about 1 cps (mPa.s) to about 50 cps (mPa.s). Cleaning compositions for rigid gas permeable contact lenses generally are more viscous than those for soft hydrogel lenses and range in viscosity from about 10 cps (mPa.s) to about 400 cps (mPa.s). One bottle cleaning, wetting and disinfecting solutions for either soft hydrogel lenses or rigid gas permeable lenses generally exhibit viscosities in the 1 cps (mPa.s) to about 50 cps (mPa.s.) range. Examples of useful viscosity builders include, but are not limited to, hydroxyethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinylalcohol and mixtures thereof. Suitable co-surfactants may be utilized in the practice of this invention and can be either cationic, anionic, amphoteric, non-ionic or mixtures thereof. The non-ionic surfactants are preferred due to their lower potential to cause ocular discomfort such as itching, burning and stinging. Examples of suitable non-ionic surfactants include, but are not limited to:

Polyoxyethylene higher fatty acid esters Higher fatty acid esters with polyoxyalkylene-polyoxyethylene copolymers

Higher fatty acid esters with polyhydric alcohols Higher fatty acid esters with polyoxyethylene polyhydric alcohols such as polyoxyethylene glyceryl fatty acid esters and polyoxyethylene sorbitan fatty acid esters Polyglycerin fatty acid esters

Polyoxyethylene alkyl ethers Polyglycerin ethers with alcohols Polyoxyethylene fatty acid amides Polyoxyethylene alkylamines Polyoxyethylene alkylphenyl ethers

Polyoxyethylene-polyoxypropylene adducts of ethylene diamine Condensate of polyoxyethylene alkylphenol ether with formaldehyde Polyoxyethylene-polyoxypropylene block copolymers Polyethyleneglycol adduct of hydrogenated castor oil

Castor oil or sterol Polyoxyethylene sorbitan fatty acid esters

The ophthalmic solutions of this invention preferably include at least one antimicrobial agent. The anti-microbial agent commonly used in ophthalmic preparations are quaternary ammonium salts such as chlorhexidine salts (CHG), benzalkonium chloride (BAK), polyhexamethylene biguanide (PHMB) and other polyquats. Another preferred anti-microbial is sorbic acid or its salt form. The quaternary ammonium compounds are generally present in concentrations ranging from about 1 to about 100 ppm, and more preferably from about 5 to about 70 ppm. The one exception is benzalkonium chloride (BAK) where the concentration utilized may be as high as 0.10% by weight. Sorbic acid (and its salts) is a weak preservative and often requires concentrations as high as 0.5%o to provide effective anti-microbial protection.

Examples of preferred anti-microbial chelating agents include ethylenediamine- tetraacetic acid (EDTA) and its salts, which are normally employed in amounts from about 0.01% to about 0.50% by weight. Other known chelating (or sequestering) agents, such as sodium citrate and nitrilo-triacetic acid can be used.

As an illustration of the present invention, several examples are provided below. A key to the ingredients used in the Examples is given in Table 1.

TABLE 1

The formulations presented in the Examples were prepared by dissolving all the ingredients in de-ionized water, with no particular order required. After the ingredients were completely dissolved, the formulation was stirred for at least two hours before the physical properties were measured.

EXAMPLE 1 The following rigid contact lens cleaning formulations (in weight %) illustrate the use of methyl glucose sesquistearate as a cleaning agent.

EXAMPLE 2 The following silicone hydrogel contact lens cleaning formulations (in weight %) illustrate the use of methyl glucose sequistearate as a biocompatible cleaning agent.

EXAMPLE 3 The following in-the-eye contact lens lubricating/cleaning formulations (in weight %) illustrate the use of methyl glucose sequistearate as a biocompatible cleaning agent.

EXAMPLE 4 An in vitro model has been developed to determine the potential for ocular irritation of both ophthalmic solutions and their components. The experimental methods follow the procedure developed by R. Tchao, which is described in "Trans- Epithelial Permeability of Fluorescein In vitro as an Assay to Determine Eye Irritants", Progress in In Vitro Toxicology, Volume 6, 1988, pages 271-283 (Mary arm Liebert, Inc. Publishers, New York), the disclosure of which is incorporated herein by reference. The Tchao technique is described as a method of determining potential eye irritation of a substance by correlating damage to a monolayer of Madin-Darby Canine Kidney (MDCK) cells with damage to corneal epithelial cells.

The amount of fluorescein passing through the cell monolayer is a function of permeability of the cell mono layer. Higher cell monolayer permeability indicates greater damage to the cell junctions from application of a test solution thereto, whereas lower cell monolayer.permeability indicates less severe damage to the cell junctions from application of the test solution. The details of the test are presented below.

Culture preparation: MDCK cells are obtained from ATCC, and maintained in minimum essential medium (MEM) supplemented with 10% bovine calf serum with iron supplementation (Hyclone, Utah). Stock cultures are passaged weekly using trypsin and EDTA. Cultures are used before passage 50. For the test, 0.5ml of a cell suspension containing 2 x 10 E5 cells are seeded in Millicell HA 13mm inserts

(Millipore, Bedford, MA). The inserts are placed in 24-well plates and fed with 0.5ml medium. Two days after seeding the cells, the media both inside and outside the inserts are replaced with fresh media. On day 6 after seeding, the inserts are used for testing the solutions. It has been shown that the resistance developed by a confluent MDCK monolayer is about 600 ohms/cm².

Test: Each insert is rinsed with Hanks Balanced Salt Solution (HBSS) 3 x 1 ml using a 10 ml syringe without needle. Each test solution (0.5 ml) is added to the inside of an insert that has been placed in a fresh 24-well plate. Triplicate inserts are used for each test solution. The 24-well plate with inserts and test solutions are placed in a humidified incubator at 37°C for 30 minutes. Each series of triplicates is handled sequentially to allow exact timing of the treatment. After incubation, sequentially, each insert is individually rinsed with HBSS 5 x 1 ml using the 10 ml syringe, and is placed in a fresh 24-well plate containing 0.5 ml HBSS in each well. 0.5 ml of a solution of Na-fluorescein (3 mg/100 ml) is added to each rinsed insert. After incubation at room temperature for 30 minutes, the inserts are sequentially removed from the wells, and the amount of Na-fluorescein in each of the wells is measured in a CytoFluor 2300, using 540 nm excitation and 590 nm emission. For each test, the negative control is HBSS and the positive control is 250 μg/ml sodium dodecyl sulfate (SDS). It has been determined that the assay can measure the effect of 50 μg/ml SDS, and the effect on the permeability of the monolayer is linearly proportional to the concentrations of SDS from 50 - 250 μg/ml. Fluorescence units (arbitrary) of each test solution is plotted against test solutions.

Interpretation of results: The results are expressed as % of SDS response, and comparisons with the HBSS response. Generally, if the solution is 20% of the SDS response, the solution may be a mild irritant.

The ocular irritation potential of methyl glucose sesquistearate was determined as well as combinations of methyl glucose sesquistearate and a block copolymer of ethyleneoxide/propyleneoxide. The following solutions were prepared and the irritation potential determined by the method detailed above.

Weight % INGREDIENT A B C

Glucamate® SSE-20 0.2 0.2 0.25

Pluronic® PI 04 - 1.00 0.75

Sodium phosphate, dibasic 0.28 0.28 0.28

Potassium phosphate, 0.055 0.055 0.055 monobasic

Sodium chloride 0.72 0.72 0.72

Disodium edetate 0.05 0.05 0.05

Dionized water (qs to) 100 100 100

The data show that both methyl glucose sesquistearate and its combination with a block copolymer of ethyleneoxide/propyleneoxide rank very close to the negative control (HBSS). Given these values, the potential for ocular irritation is minimal to non-existent.

EXAMPLE 5 A laboratory lipid soiling model has been developed to predict the ability of cleaning systems to remove lipid soils from patient worn contact lenses. The model utilizes 1000 micrograms of lipid deposited on an RGP lens or wafer sample. This level was chosen to highlight the differences between surfactants and lens cleaning products. A variety of lipid-like components, ranging form easy to remove to difficult to remove, has been included in the model. Furthermore, a fluorescent marker has been included in the lipid to follow the rate of removal and total amount of lipid removed over a fixed time interval. The lipid-like components chosen for the model were:

methyl palmitate 400 mg cholesterol oleate 300 mg phosphotidyl choline dimyristate 200 mg tributurin(glyceroltributyrate 100 mg BODIPY (marker) 1 mg

The above components were weighed and then dissolved in 10 ml of isooctane. Polished wafers (12.5 mm diameter x 0.5 mm thickness) were prepared from Boston RXD® rigid gas permeable (RGP) contact lens blanks. One surface of the wafer was then deposited with 10 micoliters of the above lipid solution. After the isooctane had evaporated the coated (1000 micrograms lipid) wafers were placed in a 45°C oven for 2-4 hours to allow the lipid to spread evenly over the surface of the wafer.

The coated sample wafers were placed into individual wells of a 24 well culture plate followed by 2.0 ml of the test solution. After 6 hours each wafer was removed from its well. The plate was then read utilizing a Cytofluor instrument at an excitation wavelength of 530 nm and an emission wavelength of 590 nm.

The fluorescent emission reading is directly proportional to the amount of lipid (marker) in the solution and can be used to gauge the ability of the test solution to remove lipid from a RGP lens surface. Alternatively, a standard curve can be constructed to convert the fluorescent readings to weight of lipid (micrograms) removed from the sample. For this model the standard curve is presented in Figure 1.

0 200 400 600 800 1000 1200

Amount of lipid, ug

Figure 1 Calibration Curve The following is a general formulation for the evaluation of the ability of a surfactant to remove soil from a RGP contact lens surface utilizing the model described above. A level of 1.0 % surfactant was chosen to amplify the differences between the surfactants tested.

Common surfactants widely used in ophthalmic solutions include polyvinylalcohol, Pluronic® F-127, Tetronic® 1107 and polysorbate 20. These surfactants were compared to both Glucamate® SSE-20 and Pluronic® P-104, all at 1.0%, using the cleaning model. The results are presented below with the results given as percent lipid removal.

The results indicate that both Glucamate® SSE-20 and Pluronic® P-104 are effective in removing lipids while the other surfactants were much less effective.

EXAMPLE 6 The following rigid gas permeable (RGP) contact lens wetting, soaking, cleaning and disinfecting solution formulation (in weight %) illustrates the use of methyl glucose sesquistearate as a biocompatible cleaning agent. Additionally, this example demonstrates the superior static cleaning ability of the methyl glucose sesquistearate based formulation when compared to two commercially available one bottle, multipurpose RGP solutions.

The previous formulation was compared to Boston® Simplicity (Bausch & Lomb) and Solo Care (Ciba Vision) in its ability to clean RGP contact lenses, in a static mode, utilizing the cleaning model detailed in Example 5. The cleaning results are as follows:

The result clearly demonstrate the superior cleaning ability of the solutions of this invention when compared to currently marketed RGP multipurpose solutions. While the invention has been particularly shown and described with reference to the preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the present invention.

Claims

What is claimed is:

1. An aqueous contact lens solution composition comprising a methyl glucose sesquistearate represented by the formula

O

II

O

wherein x + y = 15 to 25.

2. The aqueous contact lens solution of Claim 1 , wherein the solution comprises an aqueous buffered solution.

3. The aqueous contact lens solution of Claim 1 , wherein the methyl glucose sesquistearate is in an amount of from 0.01% to 5.0% by weight.

4. The aqueous contact lens solution of Claim 1 , further comprising an antimicrobial agent.

5. The aqueous contact lens solution of Claim 1, further comprising a non-ionic surfactant.

6. The aqueous contact lens solution of Claim 1, further comprising a viscosity building agent.

7. The aqueous contact lens solution of Claim 1 , further comprising a polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymer.

8. The aqueous contact lens solution of Claim 7, wherein the polyoxyethylene- polyoxypropylene-polyoxyethylene block copolymer has a molecular weight of 5000 to 7000 daltons and an HLB of 9 to 15.

9. The aqueous contact lens solution of Claim 1, having an osmolality of 200 to 350 mosm/kg.

10. The aqueous contact lens solution of Claim 1 , wherein the solution has a pH of from about 6.0 to about 8.0.

11. The aqueous contact lens solution of Claim 1 , wherein x + y = 20.

12. A method for treating contact lenses comprising: contacting a lens with an aqueous solution containing at least about 0.01 weight percent of a methyl glucose sesquistearate represented by the formula:

o

H(

O — (CC₁₇H₃₅)_{0>5 )} (H)₀.₅ wherein II x + y = 15 to 25. O

13. The method of Claim 11 , wherein the solution further comprises a buffering agent.

14. The method of Claim 11 , wherein the solution further comprises an anti microbial agent.

15. The method of Claim 11 , wherein the solution further comprises a polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymer.

16. The method of Claim 11 , comprising the sequential steps of rubbing the lens with the solution followed by rinsing with water or saline solution.

17. The method of Claim 11, comprising the sequential steps of rubbing the lens with the solution followed by immersing the lens within the solution.

18. The method of Claim 11, comprising the sequential steps of immersing the lens within the solution followed by placing the lens in the eye.

19. The method of Claim 11 , wherein x + y = 20.