GB2214328A

GB2214328A - Disinfecting contact lenses using benzoic acid

Info

Publication number: GB2214328A
Application number: GB8908923A
Authority: GB
Inventors: David John Drain; John Gordon Bernard Howes; Derek Andrew Hollingsbee
Original assignee: Smith and Nephew Associated Companies PLC
Current assignee: Smith and Nephew PLC
Priority date: 1986-03-22
Filing date: 1989-04-20
Publication date: 1989-08-31
Anticipated expiration: 2007-03-23
Also published as: GB2189045B; GB8706823D0; GB2214328B; GB8908923D0; GB2189045A

Description

DISINFECTING COMPOSITION The present invention relates to the disinfection of contact lenses and more particularly to disinfection processes which involve contacting the lens to be disinfected with an aqueous solution containing benzoic acid : to compositions used in such disinfection processes Contact lenses when worn daily can become contaminated with dirt, cosmetics, tear debris, proteins, microorganisms and the like who if they are nct rernovec fro the lens can cause irritation when the lens is replaced in the eye.

advisable, therefore, that contact lenses, and soft contact lenses in particular, are cleaned and disinfected on a regular basis, preferably daily.

it has long been recognised that the disinfection of contact lenses an soft contact lenses In particular, ss obese with problems. chemical methods have been considered. These methods reduce the propensity to cause a protein build- on the lens caused by heat disinfection methods but may instead suffer from the disadvantage that the chemical agent may concentrate in the lens. When the lens is replaced in the eye, the chemical agent may be released from the lens and damage the cornea. Certain chemical disinfectants, for example those containing halogen or halogen oxyacids, have been found to damage certain lens polymers.It would be advantageous therefore to have a cold disinfecting process for contact lenses which was especially suitable for use with soft contact lenses, in which the disinfecting means did not cause protein deposition, did not concentrate in the lens, did not affect lens polymers and could be made safe to allow direct replacement of the lens into the eye after the disinfecting process. It has been found that these criteria are met if the disinfecting process employs as the disinfecting medium an aqueous solution of - benzoic acid This process is suitable for disinfecting hard, hydrophilic (soft) and Ve permeable contact lenses particularly suitable for disinfecting soft contact lenses.

In another aspect the present invention provides a method for disinfecting a contact lens wherein the lens is contacted for a period of time sufficient to disinfect the lens with an aqueous solution containing an effective amount of benzoic acid.

In this favoured aspect the present invention provides a method for disinfecting a contact lens wherein the lens is contacted for a period of time sufficient to disinfect the lens with a solution containing an effective amount of benzoic acid and then adjusting the pH of the solution so that when the disinfected lens is removed from the solution and replaced in the eye it is non-irritant to the eye. Suitably the pH of the solution will be adjusted to the range 6 to 8.

Suitably the compositions used in the present invention will contain from 0.01 to 0.25% benzoic acid, more suitably 0.05 to 0.225% and preferably from 0.1 to 0.2%. The skilled worker will appreciate that an disinfecting effective amount of benzoic acid will vary according to the pH value of the solution which contains it, however, the compositions used in the present invention will generally contain the amounts given above. Since benzoic acid is antimicrobial only under acidic conditions the tablet or water it is dissolved in may contain an additional acidic component to provide the initial solution with a pH of from 1.8 to 5.5, more suitably 2.5 to 5.0 and preferably 2.5 to 4.5 for example 3.0 or 4.0.

Suitable acidifying agents may include sorbic, ascorbic, tartaric, lactic, acetic, fumaric, citric, maleic, adi-pic and malic acid or inorganic mineral acids such as hydrochloric or phosphoric acid.

The final composItion of the disinfectant solution may be selected so as to give a solution which is substantially isotonic that is it will have a tonicity equivalent to a 0.7 to 1.2% solution of sodium chloride. The solutions containing an effective disinfecting amount of benzoic acid are normally hypotonic and thus the tonicity cf such solutions should be adjusted > 5 the components of the neutralising system as described herein after and/or by a tonicity agent such as sodium chloride.

The period of time envisaged for disinfection of a contact lens is from 10 minutes to 8 hours. If desired the system can be used for disinfecting a lens by allowing it to stand overnight in contact with the disinfecting solution.

Since replacement of a lens into the eye from a solution of low pH value for example 1.8 to 3.2 would be irritant, it is necessary to adjust the pH of the solution containing it for example to the range 6 to 8 before the lens can be removed and replaced safely directly into the eye. This adjustment may be achieved by adding agent such as a sterile alkali solution or a tablet containing material which has an alkaline reaction with water to the solution containing the lens at the end of the disinfection cycle. There is a risk that this step may be omitted and a lens from a non-neutralised solution may be replaced in the eye.It is preferred instead to add at the beginning of the disinfection process a neutralising system: which will slol release or provide delayed release of which will adjust the p:i of the solution so that when the disinfected lens is removed from the disinfecting solutIon, the solution has a pH from 6 to 8. The adjustment of the -H of the solution may be facilitated by manually mixing the contents from time to time and especially just prior to removing the lens.

In a further aspect therefore the present invention provides an aqueous solution suitable for the disinfection of a contact lens which solution contains an effective disinfecting amount of benzoic acid.

Suitably the aqueous solutions may additionally contain an acidic component as hereinbefore described. Preferably the acidic component is tartaric acid or citric acid.

Conventionally a contact lens is disinfected by contacting it in a container, which may be closed by a screw cap, with an aqueous solution containing the disinfecting agent. The disinfecting agent may therefore be presented either in a preformed solution or as a solid form for dissolving in water. Suitable water may include distilled water, deionised water or tap water. Since benzoic acid antimicrobial only under acidic conditions the tablet or water they are dissolved in may, contain an additional acidic component to provide the initial solution with a pH of from 1.8 to 3.2, and preferably provide a pH of 2.0 to 3.0 for example 2.0, 2.5 or 3.0.

Thus the presentation of the system with which te carry out the method of the invention may include (a) an aqueous solution into which is added a tablet of the benzoic acid tablet adapted to slowly release or delayed realease a material having an alkaline reaction with water.

(b) a two layer tablet which has a rapidly dissolving layer which contains benzoic acid and optionally an acidifying agent and a slowl': dissolving or delayed release layer containing te neutralising agent. Such a tablet may be added to water in which the lens is immersed or if the acidifying agent is not present in the tablet, the tablet may be added to acidified water.

(c) an aqueous solution containing benzoic acid and an acidic component, and a slowly dissolving or delayed release tablet containing a material which has an alkaline reaction with water.

Aptly the material which has an alkaline reaction withwater may be added as a tablet and preferably one which has been adapted to provide slow or delayed release of the material, for example by encapsulation either as particles oras a tablet in a water soluble or water permeable polymer coating, in a solid matrix or in a hard slowly dissolving tablet. Suitable materials include sodium borate, carbonates and bicarbonates such as sodiu carbonate cr bicarbonate end di sodium hydrogen phosphate or other salts which ve an alkaline reaction on dissolution in water.

Preferably the alkaline material is present in a tablet which is encapsulated in a water soluble polymer coating.

Apt coatings may be formed from materials which include water soluble cellulose materials suc as hydroxyproyl ce::lose, hydroxypropyl methyl cellulose, water soluble polymers such as polyvinyl alcohol, polyacrylic acids such as those known as Carbopols (trade mark) Eudragits (trade mark). The coatings may additionally contain a more water soluble material such as lactose to facilitate the solubilisation of the coating. In a particularly preferred form the encapsulated tablet may be effervescent on exposure to water.This has the effect that as the coating dissolves from the tablet and it is exposed to water it begins to effervesce thereby mixing the contents of the container and disrupting any remaining coating so providing rapid release of the alkaline material. The skilled worker will appreciate that the thickness of the coating and its solubility will dictate the time of the delayed release of the alkaline material. Aptly the effervescence may be provided by an alkaline compound if this compound is for example a carbonate or bicarbonate such as sodium or potassium carbonate or bicarbonate. Aptly an acidic compound is also present in the tablet also to help to generate the effervescent gas. SuItable acid ^ agents incl::e citric, tartaric or maleic acids.Naturally the alkaline material will be in excess so that the pH of the solution is adjusted to pH 6 to 8.

he delayed release coating to.the tablet may be applied by many processes including the following, placing the tablet within 2 water soluble Cr water permea e envel ^e; cat the tablet by s?rayint cr fluidised bed; dip coating ::y immersing the tablet in a solution of the polymer and drying in warm air, suitable polymer solutions include hydroxypropyl cellulose in ethyl alcohol, hydroxypropyl methyl cellulose in aqueous alcohol; compression coating a tablet centred in a dry pplymer powder. Apt processes are dip coating and compression coating.Typically a Y4" tablet7 containing' the neutralising agent and/or tonicity adjusting agent may be coated by compressing in a 3/e" tablet press surrounded by a dry polymer powder. The coating so formed is about l/l6" thick and may dissolve in 2-.3 hours releasing the contents of the tablet the contents of which then dissolve.

In a further aspect the present invention comprises a part pack for producing a contact lens disinfecting solution, said part pack comprising one part an aqueous solution of an effective disinfecting amount of benzoic acid, and another part comprising a precetermined quantity cf a tablet adapted to slowly release or delay the release of a material having an alkaline react on with water.

In a further aspect the present invention comprises a two part pack for producing a contact lens disinfecting solution, said two part pac comprising a predetermined quantity tablet containing an effective disinfecting amount of benzoic acid ?.nd a slowly dissolving or delayed release neutralising agent and another part comprising a predetermined quantity of an aqueous vehicle.

The disinfecting system or the neutralising system or both may also contain a metal ion chelating agent. The chelating agent may be any compound which will chelate at least calcium and magnesium ions from tap water and which is compatible with the other components and with ophthalmic use, that is the chelating agent must be non-irritant to the eye at the concentrations used in the solution. Suitable chelating agents will include ethylene diamine tetra-acetic acid and salts thereof for example the disodiutn salt and complex polyphosphate for example sodium hexame-a?hcswhate, sodium pyrophosphate or sodium tripolyphosphate.

The chelating agent is used in an amount sufficient to remove caLcium and magnesium ions from the tap water use:: to form the disinfecting solution. The skilled worker will appreciate that the minimum amount required will vary depending upon the hardness of the tap water, a minimum amount of at least 0.01p by weight will be generally used. Suitably the amount of chelating agent used will from 0.01 to 1 % by weight, more suitably t.02 to 0.50 and preferably C.O te 0.1.

The use of the term tap water refers to water which has not been de-ionised or specially purified but is sufficiently uncontaminated to be of a potable standard. Conventionally such water is supplied as drinking water from treatment plants to a tap. This term also includes water of equivalent quality from other sources such as spring water.

Tap water may also have been chlorinated and therefore the disinfecting system may also include a dechlorinating agent. The disinfecting compositions of the present invention may use as dechlorinating agent a metabisulphite especially sodium metabisulphite.

An indicator can be included in the system so that the user may visually determine that the pH value of the disinfecting solution has been adjusted to the range 6 to 8.

The compositions employed in the method cf the inventIon ray also contain a surface active agent to assist in the cleaning and/or wetting of the lenses by the disinfecting composition. This is particularly useful when the lenses being treated are hard or gas permeable lenses Suitable surface active agents include ncn ionic surface active agents such as polyoxyethylene-polyoxypropylene diol block copolymers, scrub tan fatty acid esters, polyoxyethylated sorbitan fatty acid esters and the like. Suitably the composition may contain from 0.01 to 1Z of non-icnic surface active agent and preferable 0.05 to 0.5%.

Example 1 A solution of benzoic acid (20mg) in distilled water (lOml) is sterilised by filtration through a 0.22;m polyester filter. The final solution has a pH of 3.0 (approx). A lens is immersed in this solution in a closed container for 4 hours. At the end of this period the contents of a sachet containing anhydrous disodium hydrogen phosphate (116mg) and sodium chloride (25mg), which are previously sterilised by gamma irradiation, are added to the solution containing the lens and the container shaken to dissolve the powder. The resultant solution has a pH value of 7.4 and is approximately isotonic. The lens now disinfected is removed from the solution and is replaced in the eye.

Example 2 A sterIle solution of benzoic acid in distIlled water s prepared as described in Example 1. A lens is immersed in the solution in a closed container for 6 hours. At the end of this period a compressed tablet containing anhydrous disodium.

hydrogen phosphate (116mg) and sodium chloride (25mg) is added to the closed container and the container and contents shaken to dissolve the tablet. The final solution has a p .4 and is approximately isotonic. The disinfected lens may be removed from the solution and replaced in the eye.

Example 3 A sterile solution of benzoic acid (8ml of a solution containing 200mg in 100ml distilled water) prepared as described in Example 1 are taken and placed in a closable container. A lens is immersed in the solution in the container for 4 hours.

At the end of this period 2ml cf sterile solution of disodium hydrogen phosphate and sodium chloride (5.8g and 1.25g respectively dissolved in 100ml of distilled water and sterilised by filtration) are added to the container. The resultant solution is approximately isotonic and has a p.i of 7.2. The disinfected lens may be removed from the solution and replaced in the eye.

Claims

1 A method for disinfecting a contact lens wherein the lens is contacted for a period of time sufficient to disinfect the lens with an aqueous solution containing an effective disinfecting amount of benzoic acid.

2 A method as claimed in claim 1 in which the solution contains from 0.01 to 0.25% benzoic acid.

3 A method as claimed in either of claims 1 or 2 in which the pH of the solution is from 2.5 to 4.5.

4 A method as claimed in any one of claims 1 to 3 in which the solution additionally contains an acidic component.

5 A method as claimed in claim 4 in which the acidic component is tartaric acid.

6 A method as claimed in any one of claims 1 to 5 in which the pH value of the solution is adjusted so that when the disinfected lens is removed from the solution, the solution has a pH value of from

6 to 8.

7 A method as claimed in claim 6 in which the pH of the solution is adjusted by means of the addition to the solution of a material which has an alkaline reaction to water to the solution.

8 A method as claimed in claim 7 in which the material which has an alkaline reaction to water is present in a form which is adopted to provide slow or delayed release of the material.

9 A method as claimed in claim 8 in which the pH of the solution is adjusted by adding an effective amount of sodium hydrogen phosphate and potassium dihydrogen phosphate.

10 A method as claimed in claim 6 in which the final composition of the disinfecting solution is substantially isotonic.

11 A method as claimed in any one of claims 1 to 10 in which there is additionally present in the solution from 0.1 to 1% of a chelating agent.

12 A method as claimed in claim 6 in which there is included in the system an indicator which allows visual determination that the pH of the disinfecting solution has been adjusted to the range pH 6 to 8.

13 An aqueous solution suitable for the disinfection of a contact lens contains an effective disinfecting amount of benzoic acid.

14 An aqueous solution as claimed in 13 in which the solution contains from 0.01 to 0.25% benzoic acid.

15 An aqueous solution as claimed in either of claims 13 to 16 in which the solution additionally contains an acidic component.

16 An aqueous solution as claimed in claim 15 in which the acidic component is tartaric acid.

17 An aqueous solution as claimed in anyone of claims 13 to 16 in which the solution contains from 0.1 to 1% of chelating agent.

18 An aqueous solution as claimed in any one of claims 13 to 17 in which the solution contains an indicator which allows visual determination that the pH value of the disinfecting solution has been adjusted to the range pH6 to 8.