AU721520B2 - Carbohydrate composition and method for cleaning and disinfecting contact lenses - Google Patents

Description

S F Ref: 342418D1

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT

ORIGINAL

4* 4 .4 4 Name and Address of Applicant: Actual Inventor(s): Address for Service: Invention Title: Bausch Lomb Incorporated One Chase Square P.O. Box 54 Rochester New York 14601-0054 UNITED STATES OF AMERICA Suzanne F. Groemmlnger and Rick Panlcucci Spruson Ferguson, Patent Attorneys Level 33 St Martins Tower, 31 Market Street Sydney, New South Wales, 2000, Australia Carbohydrate Composition and Method for Cleaning and Disinfecting Contact Lenses The following statement Is a best method of performing it full description known to me/us:of this invention, including the 5845 CARBOHYDRATE COMPOSITION AND METHOD FOR CLEANING AND DISINFECTING CONTACT LENSES BACKGROUND OF THE INVENTION FIELD OF THE INVENTION The field of this invention is cleaning contact lenses using carbohydrate compositions. More oparticularly, the invention relates to compositions and methods that combine cleaning using certain carbohydrates with thermal or chemical disinfecting of contact lenses.

DESCRIPTION OF THE ART In the normal course of wearing contact lenses, tear film and debris consisting of proteinaceous, oily, sebaceous and related organic manner have a tendency to ;odeposit and build up on lens surfaces. As part of a routine care regimen, contact lenses must be cleaned to remove these film deposits and debris. Without proper cleaning and removal of deposits, wettability and optical quality of the lenses are reduced causing discomfort for the wearer and reduced visual clarity, respectively.

-2- Further, contact lenses, especially those made from hydrophilic materials, must be frequently disinfected to kill harmful microorganisms that collect or grow on lens surfaces. A number of methods for disinfecting contact Slenses have been used, such as subjecting the lenses to high temperature, oxidative chemicals or various antimicrobial agents.

Conventionally, the cleaning of contact lenses is o accomplished by one or both of two general classes of cleaners, based on surfactants or enzymes. Surfactant cleaners are effective for the removal of some carbohydrate and lipid derived matter and are typically recommended for daily use. However, these cleaners are only slightly effective in the removal of proteinaceous matter, such as lysozyme, a principal component of tears. Typically, proteolytic enzymes, derived from plant, animal or microbial sources, are used to remove proteinaceous deposits. These enzyme cleaners are w typically recommended for cleaning lenses once per week at ambient temperatures.

The process of cleaning and disinfecting contact lenses conventionally requires two or more steps.

,L Cleaning typically requires soaking in a cleaning solution of surfactant or enzyme at ambient temperature 4- r, -3for a sufficient period to effectively remove deposits.

Disinfection involves contacting the lenses with a solution containing antimicrobial agents at ambient temperatures or exposing the lenses in an aqueous to elevated temperatures for a time sufficient to achieve disinfection.

Those developing contact lens care products seek to simplify lens care regimens used by lens wearers. As indicated above, a lens care regimen will typically include a number of steps in combination that must be followed to effectively clean and disinfect. It is commonly known that lens wearers often fail to follow complex cleaning and disinfecting methods. Since many of the chemicals utilized in the process, as well as contaminating microorganisms, are harmful to the eye, compliance is an important concern. It is also a goal that the cleaned and disinfected lens, at the end of a one-step regimen, reside in a substantially isotonic o solution of such a character that the lens may' be inserted directly into the eye without further rubbing and rinsing to remove potentially harmful materials.

Ideally, contact lens cleaning/disinfecting regimens would be reduced to a single step. However, combining Scleaning and disinfecting in a single step has proved to be difficult to achieve because of competing reactions involved and the nature of the chemicals conventionally used.

Cleaning of proteinaceous deposits from contact Slenses has evolved primarily into the use of enzymes that effectively remove this type of contaminant that binds to lens surfaces. Since enzymes may not be safely placed in the eye at the end of the lens cleaning step, they must be removed or deactivated prior to wearing.

Since enzymatic cleaners do not substantially disinfect contact lenses, there must be a disinfection step in the regimen. As described above, the disinfection step may be chemical in nature or employ elevated temperature.

At the completion of chemical disinfection, it is generally necessary to either neutralize or rinse residual chemicals from the lens surfaces before they may be safely inserted in the eye. For example, in Huth et al, U.S. Re 32,672, contact lenses are simultaneously lo cleaned and disinfected by placing them in a solution containing an enzyme and hydrogen peroxide. At completion of the cleaning/disinfecting cycle, residual hydrogen peroxide must be decomposed or neutralized before the lenses can be placed on the eye. A rub and 2, rinse step with an isotonic buffered saline solution is often recommended after neutralization as a final step s before insertion of the cleaned and disinfected lenses into the eye.

In U.S. 5,096,607, contact lenses are simultaneously cleaned and disinfected by contacting the lenses with an aqueous system containing a disinfecting amount of an antimicrobial agent, such as a polymeric quaternary ammonium salt or biguanide, and an effective amount of a proteolytic enzyme. The osmotic value of to this system is adjusted such that the activity of the antimicrobial agent is not inhibited. While the lenses do not need a separate chemical neutralizing step, they must be rinsed with a suitable isotonic aqueous solution prior to insertion in the eye to remove any residual K enzyme therefrom.

Another commonly accepted technique for disinfecting contact lenses after cleaning employs a thermal disinfection process in which the lenses are zoplaced in a solution and elevated in temperature for a period of time sufficient to effect the disinfection.

In Ogunbiyi et al, U.S. 4,614,549, cleaning and disinfection are accomplished simultaneously by placing the lenses in a solution comprising a proteolytic enzyme Z-dissolved in water at about room temperature and then heating the solution and lenses to an elevated -6temperature of about 60-100*C for about 60 minutes or less. The temperature increase first activates the enzyme to accomplish the cleaning. As the process proceeds, the enzyme is deactivated and removed protein f denatured to form a suspended particulate precipitate.

The lenses must be rubbed and rinsed prior to insertion in the eye to remove any precipitated protein therefrom.

The thermal disinfection technique, of course, requires S a special electrical disinfecting apparatus.

There is a continuing need for new cleaning and disinfecting compositions and methods that permit simple cleaning regimens. The formulation of one-step cleaning and disinfecting systems that would allow one to place the cleaned and disinfected lens directly in the eye without prior rinsing or rubbing is always a principal goal.

Summary of Invention It has now surprisingly been found that certain carbohydrate cleaning solutions that are safe for use in the human eye are effective for cleaning proteinaceous deposits from contact lenses. Preferred carbohydrates are certain mono or disaccharides, or an alcohol or a partially hydrolysed ester of such saccharides or mixtures thereof. Such preferred carbohydrates include, but are not limited to, sorbitol, glucose, maltose, sucrose, dulcitol, dextran, dextrin, mannitol, maltitol, mannose or mixtures thereof in an aqueous solution in an effective amount.

There is disclosed herein an aqueous solution for simultaneously cleaning and disinfecting contact lenses, which solution is not an enzyme cleaner and comprises: a cleaning component comprising from about 0.001 to about 10 weight percent of a carbohydrate selected from the group consisting of glucose, maltose, sucrose, maltitol, mannose, and mixtures thereof, and an effective amount of at least about 0.00001 percent by weight of an antimicrobial agent, wherein said composition is safe for direct eye contact.

There is further disclosed herein an aqueous solution for simultaneously cleaning and disinfecting contact lenses, which solution is not an enzyme cleaner and comprises: a cleaning component comprising from about 0.001 to about 10 weight percent of a carbohydrate that is a di-saccharide or an alcohol or partially hydrolysed ester of such 20 saccharides and mixtures thereof, and an effective amount of at least about 0.00001 percent by weight of an antimicrobial agent, wherein said composition is safe for direct eye contact.

Further disclosed is a method for one-step cleaning and disinfecting of a contact lens, including the removal of proteinaceous contaminants, that does not use an enzyme 25 cleaner, which method comprises: contacting said contact lens with an aqueous solution comprising: a cleaning component comprising from about 0.001 to about weight percent of a carbohydrate selected from the group consisting of Ssorbitol, glucose, maltose, sucrose, dulcitol, dextran, dextrin, mannitol, maltitol, mannose, and mixtures thereof, and (ii) an effective amount of at least about 0.00001 percent by weight of an antimicrobial agent, and placing said contact lenses directly in the eye after contacting said lens with said aqueous solution.

Also disclosed is a method for one-step cleaning and disinfecting of a contact lens, including removal of proteinaceous contaminants, that does not require an enzyme, which method comprises: contacting said contact lens with an aqueous solution comprising: [n:\libaa]01474:tab a cleaning component comprising from about 0.001 to about weight percent of a carbohydrate that is a mono- or di-saccharide or an alcohol or partially hydrolysed ester of such saccharides and mixtures thereof, and (ii) an effective amount of at least about 0.00001 percent by weight of an antimicrobial agent, and placing said contact lenses directly in the eye after contacting said lens with said aqueous solution.

An effective amount of said carbohydrates of the invention is about 0.001 to about weight percent in an aqueous solution. The solution may include buffer compounds such as borate or phosphate buffers to regulate pH. A preferred composition for cleaning comprises sorbitol in an amount of about 0.1% to about 1% by weight in an aqueous solution.

The invention also comprises a method for simultaneously cleaning and disinfecting contact lenses comprising contacting said lenses with a composition comprising a carbohydrate that is a mono or o o

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o [n:\libaa]01474:tab -8disaccharide, or an alcohol or a partially hydrolyzed ester of such saccharide or mixtures thereof.

Preferably, said carbohydrate comprises sorbitol, glucose, maltose, sucrose, dulcitol, dextran, dextrin, smannitol, maltitol or mannose, wherein the composition comprises about 0.001 to about 10 weight percent of said carbohydrate, and said lenses are contacted for a sufficient time to effectively clean said lenses. After cleaning is complete, the solution containing the lenses Lois then preferably elevated to a temperature of at least about 60*C, for a time sufficient to complete cleaning and disinfecting of lenses.

In an alternative embodiment of the method for rsimultaneously cleaning and disinfecting contact lenses, the lenses are contacted with a solution containing above-noted carbohydrate and a disinfecting amount of an antimicrobial agent, for a time sufficient to clean and disinfect the lenses.

DETAILED DESCRIPTION OF THE INVENTION The present invention can be used with all contact lenses, such as hard, soft, rigid gas-permeable and 2s silicone lenses, and is particularly advantageous for cleaning and disinfecting soft lenses such as those commonly referred to as hydrogel lenses. The hydrogel lenses are typically prepared from monomers such as hydroxyethylmethacrylate, vinyl-pyrrolidone, glycerol methacrylate, methacrylic acid or acid esters and the slike. Hydrogel lenses absorb significant amounts of water, such as about 4 to 80% by weight, and bind significantly higher amounts of contaminating proteins than other types of lenses.

o The compositions employed herein for cleaning contact lenses contain one (or more) of a carbohydrate Sthat is a mono- or disaccharide, or a sugar alcohol or a partially hydrolyzed ester of such saccharide or mixtures thereof. Preferred carbohydrates are sorbitol, 5 glucose, maltose, sucrose, dulcitol, dextran, dextrin, mannitol, maltitol or mannose. The most preferred composition comprises sorbitol.

The present invention employs the selected io carbohydrate or mixtures thereof in an effective amount to clean the lenses. An effective amount is that required to remove, in a reasonable time, a substantial portion of the proteinaceous deposits that occur during normal wear of contact lenses. The carbohydrates of the invention will be effective in an amount of about 0.001 to about 10%. A preferred amount is about 1.0 weight percent of the aqueous cleaning solution. The precise amount of the carbohydrate required to efficaciously clean contact lenses will depend upon a number of factors, including the carbohydrate selected, the amount of proteinaceous deposit on the lenses, the desired soaking period, the specific type of materials comprising the lenses, other cleaning solution and disinfecting components and the like. In general, as appreciated by those skilled in the art, the \ocarbohydrate concentrations useful herein will be adjusted to achieve a desired time for removing the proteinaceous contaminants.

The compositions of the present invention may contain additional components that do not adversely affect, to any significant extent, the activity of the selected carbohydrate cleaner. Illustrative examples of *0*0 such components typically found in ophthalmic solutions include one or more suitable antimicrobial agents, 2o buffering agents, chelating and/or sequestering agents, a tonicity adjusting agent and surfactants.

The carbohydrate composition may contain a preserving or disinfecting amount of one or more antimicrobial agents that are compatible with and do not adversely affect the activity of the carbohydrate or -11other components. Suitable chemical antimicrobial agents, as the term is used herein, include quaternary ammonium salts and polymers used in ophthalmic applications such as poly [(dimethyliminio)-2-butene- 1,4-diyl chloride], [4-tris(2-hydroxyethyl) ammonio]-2butenyl-w- [tris(2-hydroxyethyl) ammonio] dichloride, generally available as Polyquaternium I* from Onyx Corporation, benzylkonium halides, trialkylammonium halides, biguanides such as hexamethylene biguanides and to their polymers, oxidizing agents and the like.

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Preferably, the disinfecting antimicrobial agent is one which alone or in combination will reduce the microbial burden by about one log order in one hour and, more preferably, by about two log orders in four hours.

1Typically, such agents are present in concentrations ranging from about 0.00001% to about 0.5% and more preferably from about 0.00003% to about 0.05% Alternatively, the disinfecting process of the .o invention is accomplished by thermal means conventionally employing a suitable thermal disinfecting apparatus such as taught by Ogunbiyi et al in U.S.

4,614,549, which is incorporated herein by reference.

z. The compositions of the present invention can be prepared in various physical forms, such as liquids, -12solids, emulsions or colloidal suspensions. For example, the carbohydrates and additional ophthalmologic ingredients can be dissolved or suspended in a suitable solvent such as water, glycerol, propylene glycol or the s like so long as such carriers and ingredients are compatible with direct insertion into the eye, where such is the intended regimen. Alternatively, the composition can be in the form of a powder or tablet wherein the latter will typically contain binders or c* i oother tablet excipients.

The following detailed examples are presented to illustrate the present invention. Both ambient and thermal cleaning processes are performed on the indicated lenses, identified by FDA group characteristics.

EXAMPLE 1 Ten SoftMateo B lenses manufactured by Sola/Barnes- Hind of bufilcon A polymer having a 45% water content (FDA Group III), are soaked for 1 hour in lysozyme at 37'C in order to deposit protein on the lens, simulating lens wear. Each lens is then placed in a test cleaning 2. solution in a thermal disinfection unit (TDU) and a TDU disinfection cycle completed. The lysozyme soak and TDU -13disinfecting/cleaning cycle are repeated for seven cycles. Following the last cycle, each lens is soaked in 10 ml of borate buffered saline solution for one hour followed by analysis for total protein utilizing the Ninhydrin procedure, described by G. Minno, L. Eckel, S.

Groemminger, B. Minno and T. Wrzosek, in "Quantitative Analysis of Protein Deposits on Hydrophilic Contact Lenses", Optometrv and Vision Science, Vol. 68, No. 1, pp. 865-872.

The test solutions are each prepared with borate buffered saline solution at pH 7.0 7.2 and osmolality of 290-310 mOsm/kg water. The borate buffered saline consists of 0.85% boric acid, 0.09% sodium borate and 5 i 0.45% sodium chloride. Cleaning results are reported in Table 1.

TABLE 1 Simultaneous Cleaning and Thermal Disinfection of Bufilcon Group 3 Contact Lenses Residual Protein Cleaning Conc. on Lens Increased Removal Compound [pg/lens] Over Control [%1 Sorbitol 1% 10.69 58.4 Glucose 1% 18.76 27.1 Borate Buffered 25.72 Saline (Control) -14- A seven cycle ambient cleaning efficacy test is performed for ten new Vistamarc (FDA Group IV) contact s lenses, manufactured by Johnson Johnson Vision Products Inc. of Etaficon A polymer having a 58% water content. The lenses are soaked for one hour in lysozyme at 37°C in order to deposit protein on the lenses, simulating lens wear. Each lens is placed in 10mL of tothe test cleaning solution and soaked for 4 hours. Any protein remaining on the lens is heat fixed after each cycle. The protein deposition and cleaning regimens are repeated for seven cycles. The buffer system is either borate (same as Example 1) or phosphate based. The 1 phosphate buffered saline consists of 0.30% sodium phosphate, dibasic; 0.03% sodium phosphate, monobasic; and 0.85% sodium chloride. Cleaning efficacy results are reported in Table 2.

Contact Lens Cleaning Efficacy for Vistamarc (FDA Group IV) Lenses at Ambient Temperature Cleaning Compound Control (BBS)* 1% Sorbitol in BBS 1% Dulcitol in BBS 1% Sorbitol in PBS** 1% Dulcitol in PBS Residual Protein on Lens (6q) 780 721 654 481 509 Increased Removal over Control r%1 7.6 16.2 38.3 34.7 BBS Borate Buffered Saline PBS Phosphate Buffered Saline The results of Table 2 show that selection of buffer may influence cleaning efficiency, depending upon the carbohydrate cleaner selected.

o EXAMPLE 3 The procedure of Example i is repeated for a cleaning solution of the invention including 1% by weight of sorbitol in borate buffered saline for cleaning various FDA group lens. All formulations are prepared with borate buffered saline (BBS), at a pH of -16r 7.0-7.3 and osmolality of 280-320 mOsm/kg., as described in Example 1. Cleaning results are report in Table 3.

TABLE 3 SContact Lens Cleaning Efficacy for Various FDA Group Lens Increased Test FDA Lens pg Protein Removal Over Compound Grou Per Lens Control [%1 1% Sorbitol in BBS II 13 32 BBS Control II 19 1% Sorbitol in BBS 1 III 5 54 BBS Control III 11 1% Sorbitol in BBS IV 682 18 BBS Control IV 827 1% Sorbitol +0.025% III 7 36 EDTA in BBS BBS Control EDTA III 11 1 Borate Buffered Saline 2 Ethylenediaminetetracetic acid, disodium salt EXAMPLE 4 SoftMate* B contact lenses are soaked in a protein deposition solution containing 0.1% her/lysozyme for one hour at 37 C. The lenses are removed from the protein solution and are thermally cleaned/disinfected in a 21 buffered isotonic solution containing the indicated test cleaning compounds. After the thermal cycle is -17complete, the lenses are removed from the test solution.

The deposit/cleaning cycles are repeated for a total of 7 cycles. The total protein remaining on the lenses is determined using the Ninhydrin method. Ten lenses are for each cleaning solution. The results for borate buffered solutions are reported in Table 4.

TABLE 4 Protein Cleaning Efficacy Evaluation of Some Carbohydrates of the Invention on Group III Lenses Cleaning Compound BBS* Control 1% Dextrin 1% Dextran 1% Sorbitol 0.1% Sorbitol 1% Mannitol BBS* Control 1% Maltose 1% Mannose 1% Sucrose 1% Dulcitol Residual Protein On Lens [ug/lens 8.4 6.1 5.5 4.0 5.5 6.1 12.5 7.7 13.8 9.2 6.4 Increased Removal Over Control [%1 27 34 52 34 27 Borate buffered saline

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-18- EXAMPLE r oo oao o The procedure of Example 1 is repeated for FDA Group I lenses. Each lens is contacted with the indicated test solutions and is processed through seven protein deposit and thermal/cleaning cycles. The results are reported in Table TABLE Protein Cleaning Efficacy Evaluation of Some Common Carbohydrates on Group I Lenses Residual Residual Increased Protein, Protein, Removal Cleaning pg/lens pg/lens Over Compound Buffer Test Control Control [%1 1% Sorbitol BBS 0.8 3.2 1% Mannitol BBS 2.9 3.3 12 1% Maltitol BBS 3.2 3.3 4 1% Mannose BBS 3.2 3.3 4 1% Sucrose BBS 2.1 2.9 28 1% Dextran BBS 2.0 3.2 38 1% Dextrin BBS 1.5 3.2 53 1% Sorbitol PBS 0.8 3.2 1% Manitol PBS 3.2 3.3 4 1% Maltitol PBS 2.7 3.3 18 1% Mannose PBS 3.1 3.3 6 1% Sucrose PBS 2.2 2.9 24 1% Dextran PBS 1.0 3.2 69 1% Dextrin PBS 1.3 3.2 59

Claims (10)

1. An aqueous solution for simultaneously cleaning and disinfecting contact lenses, which solution is not an enzyme cleaner and comprises: a cleaning component comprising from about 0.001 to about 10 weight percent of a carbohydrate selected from the group consisting of glucose, maltose, sucrose, maltitol, mannose, and mixtures thereof, and an effective amount of at least about 0.00001 percent by weight of an antimicrobial agent, wherein said composition is safe for direct eye contact.

2. An aqueous solution for simultaneously cleaning and disinfecting contact 1 o lenses, which solution is not an enzyme cleaner and comprises: a cleaning component comprising from about 0.001 to about 10 weight percent of a carbohydrate that is a di-saccharide or an alcohol or partially hydrolysed ester of such saccharides and mixtures thereof, and an effective amount of at least about 0.00001 percent by weight of an antimicrobial agent, wherein said composition is safe for direct eye contact.

3. The aqueous solution of claim 2, wherein said cleaning component is selected from the group consisting of maltose, sucrose, maltitol, and mixtures thereof.

4. The aqueous solution of any one of claims 1 to 3, further comprising a buffering agent and a tonicity adjusting agent.

5. The aqueous solution of any one of claims 1 to 4, further comprising a surfactant.

6. A method for one-step cleaning and disinfecting of a contact lens, including the removal of proteinaceous contaminants, that does not use an enzyme cleaner, which method comprises: 9 9 .9 9 9* 9 *9999 9 9.

9. 7. removal comprise contacting said contact lens with an aqueous solution comprising: a cleaning component comprising from about 0.001 to about weight percent of a carbohydrate selected from the group consisting of sorbitol, glucose, maltose, sucrose, dulcitol, dextran, dextrin, mannitol, maltitol, mannose, and mixtures thereof, and (ii) an effective amount of at least about 0.00001 percent by weight of an antimicrobial agent, and placing said contact lenses directly in the eye after contacting said lens with said aqueous solution. A method for one-step cleaning and disinfecting of a contact lens, including of proteinaceous contaminants, that does not require an enzyme, which method s: contacting said contact lens with an aqueous solution comprising: a cleaning component comprising from about 0.001 to about weight percent of a carbohydrate that is a mono- or di-saccharide or an [n:\libaa]01474:tab alcohol or partially hydrolysed ester of such saccharides and mixtures thereof, and (ii) an effective amount of at least about 0.00001 percent by weight of an antimicrobial agent, and placing said contact lenses directly in the eye after contacting said lens with said aqueous solution. 8. The method of claim 7, wherein said cleaning component is selected from the group consisting of sorbitol, glucose, maltose, sucrose, dulcitol, mannitol, maltitol, mannose, and combinations thereof. 9. The method of claim 7 or claim 8, wherein said cleaning component is sorbitol. The method of any one of claims 7 to 9, wherein said solution further comprises a buffering agent and a tonicity adjusting agent.

11. The method of any one of claims 7 to 10, wherein the solution further comprises a surfactant.

12. The method of any one of claims 7 to 11, wherein the method does not require :o rubbing. S13. An aqueous solution for simultaneously cleaning contact lenses, which solution is not an enzyme cleaner and is substantially as hereinbefore described with 20 reference to any one of the Examples but excluding the Comparative Examples.

14. A method for one-step cleaning and disinfecting of a contact lens including the removal of proteinaceous contaminants, that does not use an enzyme cleaner, which method is substantially as hereinbefore described with reference to any one of the Examples but excluding the Comparative Examples. 25 15. A method for one-step cleaning and disinfecting of a contact lens including the S removal of proteinaceous contaminants, that does not use an enzyme cleaner, which method comprises contacting said contact lens with an aqueous solution which is substantially as hereinbefore described with reference to any one of the Examples but excluding the Comparative Examples. Dated 20 January, 1999 Bausch Lomb Incorporated Patent Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON [n:\libaa]01474:tab