Method and composition for disinfecting contact lenses.

PROCESS FOR PREPARING A COMPOSITION TO DISINFECT CONTACT LENS CONTAINING TROMETAMIN OR ITS SALTS

DESCRIPTIVE MEMORY

resume

The present invention relates to a method for disinfecting a contact lens which comprises contacting said lens with an isotonic aqueous solution comprising 0.6 to 2% by weight of tromethamine (preferably 0%). 8 to 1.5%) for a sufficient time to disinfect them. In another aspect of the method, solutions are added to which 0.01 to 1% by weight of a chelating agent (preferably disodium EDTA) and / or additional microbicide is added.

The invention also relates to the process for preparing the compositions used in said method.

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A soft contact lens disinfectant must have, in combination, the following properties:

(1) must perform the required disinfection and (2) must be harmless to soft contact lenses and (3a) any remaining lens after disinfection must be harmless to the eye of the contact lens wearer or (3b) must be capable of be neutralized to a harmless form before use by the lens wearer.

Three per cent hydrogen peroxide adequately meets requirements (1), (2) and (3b). However, the neutralization step is considered undesirable by many users. Hence it is even more desirable to obtain a disinfectant that meets the requirements (1), (2) and (3a).

International Patent Publication No. WO 91/01763 discloses that solutions having very low concentrations of peroxide, i.e. 0.01 to 0.5%, more preferably 0.05 to 0.2%, can provide unnecessary disinfection. of neutralization. The present invention contributes greatly to the microbicidal efficacy of peroxide at such low concentrations.

US Patent No. 4,758,595 (Ogunbiyi, et al) discloses that polyhexamethylene biguanide (PHMB) and its water-soluble salts may perform minimal disinfection and be

<img file="PT99893B_D0002.tif" />

harmless to the eye and lens if used with a specific buffer, surfactant and at specific concentrations.

The present invention in its preferred aspects has superior disinfecting properties and is substantially non-irritating as clinically observed. The present invention is based on the surprising discovery that tromethamine and its salts, in suitable concentration, are a bactericidal and fungicidal. In addition, tromethamine has a synergistic effect when combined with other known microbicides and chelating agents.

The present invention can be summarized as a method of disinfecting a contact lens, which is to contact the lens with an aqueous isotonic solution containing 0.6 to 2% by weight of tromethamine (preferably 0.8 1.5%) for a sufficient time to disinfect the lens. Other aspects include the addition of 0.01 to 1% by weight of chelating agent (preferably disodium EDTA) and / or additional microbicide (preferably 0.00001 to 0.1% by weight) of PHMB N-alkyl-2-pyrrolidone, chlorohexidine, polyquaternium-1, hexetidine, bronopol, alexidine, low concentration peroxide, and their ophthalmically acceptable salts.

The term ophthalmologically acceptable, when used to describe salts, etc., in this specification and claims is intended to mean a compound which is soluble in solution at its effective concentration and which is not harmful to the eye or lens. Examples of ophthalmologically acceptable ingredients are given throughout the specification. It is evident that the use of ophthalmologically acceptable ingredients is within the scope of this invention.

X

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The present invention has the advantage of providing a method and composition for disinfecting contact lenses covering a wide range of microorganisms such as Fusarium solani, Aspergillus fumigatus, Staphylococcus epidermis, Pseudomonas aeruginosa, Serratia marcescens, Candida albicans and Herpes simplex. Of these, it has been found to be particularly difficult to disinfect S. marcescens and C. albicans in lenses having prior art compositions. 0 The present invention also has the advantage of providing a method and composition for disinfecting contact lenses that is compatible, and which has little or no undesirable chemical reactions with hydrophilic contact lenses. Another advantage of the present invention is that it provides a method and composition for disinfecting contact lenses with poor potential for eye irritation. And yet another advantage of the present invention is that, in certain embodiments, it provides a method and composition for disinfecting contact lenses, for cleaning tear drop film on contact lenses, and for lubricating contact lenses. contact.

Tromethamine, whose chemical name is 2-amino-2-hydroxymethyl-1,3-propanediol, is also known by the names trimethylol aminomethane; tris (hydroxymethyl) aminomethane; trisamine; tris buffer solution; trometamol; Tromethane; THAM; TRIS; talatrol; Tris-Amino; Tris-sterile; Trizma as described in Merck Index. Ed. 11, published by Merck &amp; Co., Inc. Rahway, NJ (1989). Tromethamine and its salts act as buffer solutions over the pH range of 6-9. In Technical Bulletin TB 69, TRIS AMINO® as a pH control buffer solution from ANGUS Chemical Company, it is disclosed that TRIS AMINO maintains the pH of contact lens solutions in the most favorable range for hydrolyzing protein films on lens surfaces. , and that the absence of eye irritation caused by TRIS AMINO is of the highest

<img file="PT99893B_D0004.tif" />

importance in your choice for this application. However, the ANGUS Technical Bulletin does not contain the disclosure of the use of tromethamine in the formulation of contact lens disinfection solutions, the fact that tromethamine has microbicidal properties, or the fact that tromethamine has a synergistic effect when in combination with other microbicides.

Ophthalmologically acceptable chelating agents useful in the present invention include amino carboxylic acid compounds or water soluble salts thereof, including ethylene diamine tetraacetic acid, nitrile triacetic acid, diethylene triamine pentaacetic acid, hydroxyethyl ethylene diamine acid, triacetic acid, 1,2-diaminocyclohexane tetraacetic acid, ethylene glycol bis (beta-aminoethyl ether) in Ν, Ν, Ν ', Ν' tetraacetic acid (EGTA), amino diacetic acid and hydroxyethyl amino diacetic acid. These acids may be used in the form of their water-soluble salts, in particular their alkali metal salts. Especially preferred chelating agents are di-, tri-, and tetrasodium salts of ethylenediamine tetraacetic acid (EDTA), most preferably disodium EDTA (Edetate Disodium).

Other chelating agents such as citrates and polyphosphates may also be used in the present invention. Citrates which may be used in the present invention include citric acid and its mono-, di- or tri-alkali metal salts. Polyphosphates that may be used include pyrophosphates, triphosphates, tetraphosphates, trimetaphosphates, tetrametaphosphates, as well as more highly condensed phosphates in the form of neutral or acidic alkali metal salts, such as sodium and potassium salts, as well as ammonium salt.

The pH of the solutions should be adjusted to be compatible with the eye and contact lens, particularly for

<img file="PT99893B_D0005.tif" />

between 6.0 and 8.0, preferably between 6.8 and 7.8. Significant deviations from the neutral value (pH = 7) will cause changes in the physical parameters (ie diameter) in some contact lenses. A low pH (below 5.5 may cause inflammation and eye sting, while too low or too high a pH (below 3.0 or above 10) may cause eye damage.

The term disinfect means to render virtually all pathogenic myocrobes in the vegetative state unviable, including gram negative and gram positive bacteria as well as fungi.

Additional microbicides used in the present invention are known, namely polyhexamethylene biguanide, N-alkyl-2-pyrrolidone, chlorohexidine, polyhexamethylene biguanide, alexidine, polyquaternium-1, hexetidine, bronopol, hydrogen peroxide in a concentration too low, p. eg 50 to 200 ppm.

The solutions of the invention are compatible with both gas permeable rigid and hydrophilic contact lenses during cleaning, wetting, soaking, rinsing and disinfecting processes.

One embodiment of the invention is a combination of dry, solid, dispersible or water soluble unit dosage forms, for example tablets. One type of tablet would contain tromethamine or its salt, the microbicide and the chelating agent. Prior to use, the tablet is dissolved in the diluent, for example water or saline, to form a solution for disinfecting contact lenses. Another form of

<img file="PT99893B_D0006.tif" />

One embodiment of the invention would be an aqueous solution comprising the novel disinfectant ingredients.

A typical aqueous solution of the present invention may contain additional ingredients that would not affect the basic and novel characteristics of the previously described active ingredients, namely tonicity agents, surfactants and viscosity inducing agents, which may contribute to both lens cleaning and provide lubrication to the eye. Suitable tonicity agents include sodium chloride, potassium chloride, glycerol or mixtures thereof. The solution tonicity is typically adjusted to approximately 240-310 milliosmoles per kilogram of solution (mOsm / kg) to make the solution compatible with ocular tissue and hydrophilic contact lenses.

Suitable surfactants include tiloxapol, which is a 4- (1,1,3,3-tetramethyl-butyl) phenol polymer with formaldehyde and oxirane; pluronic or ploxamers, nonionic block copolymer surfactants, which are block copolymers of propylene oxide and ethylene oxide; octoxynol or octiphenoxy polyethoxyethanol prepared by reaction of isooctyl phenol with ethylene oxide; poloxamine, which is a block copolymer derivative of ethylene oxide and propylene oxide combined with ethylene diamine; and nonoxynol nonionic surfactant mixtures prepared by reacting nonyl phenols with ethylene oxide. Most of these surfactants are described in the above Merck Index. The surfactants may be used in amounts ranging from about 0.0001 to about 20% by weight, preferably from about 0.005 to about 5.0% by weight, more preferably from about 0.025 to about 20% by weight. 1% by weight.

Suitable viscosity inducing agents may include lecithin or cellulose derivatives such as

<img file="PT99893B_D0007.tif" />

hydroxy methyl cellulose, hydroxy propyl cellulose and methyl cellulose in amounts similar to the above surfactants.

If solid dosage forms are used, the formulations may include conventional lubricants, binders, and excipients which include, but are not limited to, glycerol, sorbitol, propylene glycol, polyethylene glycols and dextran. These materials are used in amounts ranging from 0.001 to 30% by weight, preferably from about 0.1 to 5%.

Preferred aqueous solutions of the invention may be prepared by adding the ingredient, namely: Tromethamine is added to water. The pH of the solution is adjusted to about 6.8 to about 7.8. Chelating agent and tonicity agent are added, if desired. Stir until the above ingredients dissolve. Eventually, the surfactant and the viscosity inducing agent are added. The microbicide is added. 0 end product may be rendered sterile by sterile filtration, hot sterilization or a combination thereof.

A suggested method for disinfecting a contact lens is as follows: The lens is first rubbed with a few drops of rubric or saline solution and rinsed to remove surface contaminants such as mucous membranes, eye paint, etc., and then placed. in a suitable container with sufficient aqueous solution to cover the lens. The lenses are soaked for at least 10 minutes and up to 8 hours until substantial extermination of the microorganisms is achieved. The above method is performed at room temperature or at elevated temperatures, i.e. 20 ° C to about 100 ° C.

To illustrate how the invention may be carried out, the following examples are given. It is evident, however, that the examples are for illustration purposes but should not be construed as limited to any of the spatial materials or conditions indicated therein. The term qs means quantum sufficiat or a volume sufficient to make up the volume of the aqueous solution. Unless otherwise indicated, it means weight per unit volume expressed as a percentage (w / v).

Disinfectant efficacy was determined by inoculating the test solution with a microbial suspension at a concentration of

approximately 10 colony forming units per ml. Each inoculated solution was then vigorously stirred and left at room temperature.

Several times after inoculation each solution was vigorously stirred and 1 ml aliquots were taken out and distributed in 9 ml of neutralizing broth. Ten times more serial dilutions of each inoculated solution in neutralizing broth were prepared. The solutions were plated at effective 1/10 to 1 / 100,000 dilutions in nutrient agar with or without neutralizing agents. The plates were incubated under optimal duration and temperature and colony counted.

Survivor concentration and logarithmic reductions were calculated. Each tenfold reduction in concentration constitutes a logarithm reduction.

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Example 1

This example illustrates the amazing efficacy of tromethamine in an isotonic aqueous solution as a microbicide that is effective against hard-to-kill organisms.

<td>Example IA: Solution</td><td>isotonic acid containing tromethamine</td>

<td>Tromethamine</td><td> 1,2%</td>

<td>Sodium Chloride</td><td> 0,3%</td>

<td>HC1</td><td>qs ad pH 7.4</td>

<td>USP Purified Water</td><td>qs ad 100 ml</td>

Example IB:

Aqueous solution and isotonic agent containing tromethamine chelation

Tromethamine Sodium Chloride Disodium EDTA HCl

USP Purified Water

1,2%

0,3%

0,05%

qs ad pH 7.4 qs ad 100 ml

Both tromethamine solutions are prepared by dissolving the ingredients in water, adjusting the pH with hydrochloric acid and additional water to make up. Each solution is sterilized through a 0.22 micron filter.

Example 1C (Comparative):

Boric acid

Sodium Borate

Sodium Chloride Purified Water USP

Isotonic Borate Solution

1, 03%

0,19%

0,3%

qs ad 100 ml

<td>Example 1D (Comparative):</td><td rowspan="2">Isotonic Borate Solution and chelating agent</td>

<td></td>

<td>Boric acid</td><td> 1,03%</td>

<td>Sodium Borate</td><td> 0,19%</td>

<td>Sodium Chloride</td><td> 0,3%</td>

<td>Disodium EDTA</td><td> 0,05%</td>

<td>USP Purified Water</td><td>qs ad 100 ml</td>

Both ingredient solutions in water borate are prepared by dissolving them by adding water to make up. The pH of the solution is 7.4. Each solution is filter sterilized through a 0.22 micron filter.

<td>Example 2E</td><td>(Comparative):</td><td rowspan="2">Isotonic Solution</td>

<td>Phosphate</td><td>Dihydrogen</td>

<td>Sodium</td><td></td><td> 0,16%</td>

<td>Phosphate</td><td>Hydrogen</td><td></td>

<td>Disodium</td><td></td><td> 0,757%</td>

<td>Cloredo de</td><td>Sodium</td><td> 0,44%</td>

<td colspan="2">USP Purified Water</td><td>qs ad 100 ml</td>

Example 2F (Comparative):

<img file="PT99893B_D0009.tif" />

Isotonic Phosphate Solution and Chelating Agent

<td>Dihydrogen phosphate</td><td></td>

<td>Sodium</td><td> 0,16%</td>

<td>Hydrogen Phosphate</td><td></td>

<td>Disodium</td><td> 0,757%</td>

<td>Sodium Chloride</td><td> 0,44%</td>

<td>Disodium EDTA</td><td> 0,05%</td>

<td>USP Purified Water</td><td>what the</td>

Both solutions of ingredients in water, phosphate are prepared by dissolving them by adding water to make up. The pH of the solution is 7.4. The formulation for phosphate solution without chelating agent is identical to that specified in USP for isotonic ophthalmic saline. The solutions were sterilized by filtration through a 0.22 micron filter.

When tested for disinfectant efficacy, the following results were obtained:

Four Hour Logarithmic Reduction

<td>Example</td><td>S. marcescens</td><td>C. alb</td>

<td>1A (This invention)</td><td> 2,6</td><td> 1,4</td>

<td>1B (This invention)</td><td> 4,9</td><td> 1,9</td>

<td>CI (Comparative)</td><td> 0,5</td><td> &lt;0,1</td>

<td>ID (Comparative)</td><td> 0,7</td><td> &lt;0,1</td>

<td>1E (Comparative)</td><td> 0,8</td><td> &lt;0,1</td>

<td>1F (Comparative)</td><td> 0,7</td><td> &lt;0,1</td>

As can be seen, isotonic aqueous solutions containing 1.2% tromethamine reduce the concentrations of two difficult-to-kill organisms by a factor greater than 10. In addition, tromethamine has a synergistic effect when combined with a chelating agent. , Disodium EDTA. In contrast, isotonic aqueous solutions containing borate and phosphate buffered systems, with or without disodium EDTA, have significantly lower disinfection efficacy.

Example 2

This example illustrates the disinfection properties of various formulations within the scope of the invention.

<td>1 | Ex.</td><td>Tromet</td><td>1 | DiNaEDTJ</td><td>1 1 k | PHMB |</td><td colspan="2">1 OnamerMjPolyb.</td><td colspan="2">1 1 | Ty lox. | Hexet.</td><td>Ί- | CG</td><td>Oh</td>

<td>| No.</td><td>% PV</td><td>| % pv 1</td><td>| ppm | L</td><td>PPM</td><td>1 PPM J</td><td>| PPM | J_L</td><td>PPM</td><td>| PPM J</td><td>PPM</td>

<td colspan="10">1 1 I 1 1 1 1 1 1 I 1_1_1_1_1_1_1_1_1 1</td>

<td>1 2a</td><td> 0,5</td><td>1 1 0.05 I</td><td>Π Γ 1 1</td><td> 5</td><td>Ί 1 -- I</td><td>1 r 1 - 1 I 1</td><td></td><td>Ί 1" 1</td><td></td>

<td>| 2b</td><td> 0,5</td><td>1 I 0.05 I</td><td>1 1 II</td><td> —</td><td> 1 1 ⁵I</td><td>1 1 1 - 1 I 1</td><td></td><td>1 I-- 1</td><td></td>

<td>| 2c</td><td> 1,2</td><td>1 1 0.05 I</td><td>1 1 1 i 1 II</td><td></td><td>1 i - I</td><td>1 1 1 - 1 I 1</td><td></td><td>1 I-- I</td><td></td>

<td>| 2d</td><td> 1,2</td><td>1 1 0.05 I</td><td>1 1 1 i 1 I 1</td><td> —</td><td> 1 1</td><td> 1 1 1 ⁵ 1 I 1</td><td></td><td>1 I- 1</td><td></td>

<td>| 2e</td><td> 1,2</td><td> 1 | 0,05 1</td><td>1 1 1 i 1 II</td><td> —</td><td>1 I</td><td>1 1 II</td><td> 15</td><td>1 I</td><td> —</td>

<td> 1 ^2f</td><td> 1,2</td><td> 1 1 0,05 1</td><td>1 1 1 i 1</td><td> —</td><td>1 I</td><td>1 1 II</td><td> 10</td><td>1 I</td><td> —</td>

<td>| 2g</td><td> 1,2</td><td>1 1 0.05 I</td><td>1 1 1 --I I 1</td><td></td><td> 1 1 -- 1</td><td>1 1 1 - 1 1 I</td><td></td><td>1 1 50 I</td><td> —</td>

<td>| 2am</td><td> 1,2</td><td>1 I 0.05 I</td><td>1 1 1 --I I 1</td><td></td><td>1 1 -I</td><td>1 1 1 - 1 I 1</td><td></td><td>1 I-- 1</td><td> 50</td>

<td> 1 ²ⁱ 1_</td><td> 1,2</td><td>1 1 0.10 J</td><td>1 1 1 --I 1 1</td><td></td><td>1 i -1</td><td>1 1 i - 1 J_L</td><td></td><td>1 | io j</td><td> _</td>

In the previous table:

Tromet it's tromethamine

DiNaEDTA is disodium EDTA

PHMB is polyhexamethylene biguanide hydrochloride salt, a microbicide

TM TM. . TM

Onamer Μ, Polybrene and Hexetidme are microbicides.

CG is chlorhexidine glyconate, a microbicide

HA is alexidine hydrochloride, a microbicide

Tiloxapol is a surfactant.

In addition to the above ingredients, each solution contains 0.37% NaCl for isotonicity and the pH of each solution was adjusted to 7.4 with HCl.

The logarithmic reductions for various organisms after 4 hours are as follows:

<td>x.No.</td><td>Sm</td><td>If</td><td>Here</td><td>An</td><td>Af</td>

<td>2nd</td><td> 5,4</td><td> &gt;5,3</td><td> —</td><td> —</td><td> —</td>

<td>2b</td><td> 2,3</td><td> 3,6</td><td> —</td><td> —</td><td> —</td>

<td>2c</td><td> &gt;6,8</td><td> —</td><td> —</td><td> —</td><td> 1/1</td>

<td>2d</td><td> &gt;6,8</td><td> —</td><td> —</td><td> —</td><td> 1,3</td>

<td>2e</td><td> —</td><td> —</td><td> —</td><td> —</td><td> 1/6</td>

<td>2f</td><td> —</td><td> —</td><td> —</td><td> —</td><td> 1,3</td>

<td>2g</td><td> —</td><td> —</td><td> &gt;5,7</td><td> 2,0</td><td> —</td>

<td>2am</td><td> —</td><td> —</td><td> &gt;5,7</td><td> 1/2</td><td> —</td>

<td>2i</td><td> &gt;6,1</td><td> —</td><td> 1,1</td><td> —</td><td> —</td>

<img file="PT99893B_D0010.tif" />

Sm ê Serratia marcescens If it is Staphilococcus epidermidis Ca is Candida albicans

An is Aspergillus niger Af is Aspergillus fumigatus

I

Example 3

In this example, the disinfection capacity of a preferred formulation of this invention, prepared in a manner suitable for producing commercial quantities, is compared with two commercially available solutions.

Solution 3A

A commercial solution under the trademark of Optifree, described on the packaging as: a sterile, isotonic, aqueous, buffered solution containing a 0.05% disodium edetate citrate and sodium chloride buffer and POLYQUAD (polyquaternium-1) ) at 0.001% as preservatives.

&gt;

3B &amp; Solution

A commercial solution under the trademark of ReNu, Multipurpose Solution described on its packaging as:

a sterile, isotonic solution containing poloxa boric acid. . TM mine, sodium borate and sodium chloride; conserved with 0.00005% DYMED (polyaminopropyl biguanide) and 0.1% disodium edetate.

3C Solution (This invention)

Tromethamine

Naci disodium edetate

Tiloxapol

Polyhexamethylenobiguanide, HCl salt Hydrochloric acid Purified Water USP

1,2%

0,05%

0,37%

0,25%

0.0001% adjust to pH 7.5 ± 0.2 qs ad 100 ml

Tromethamine, disodium edetate and sodium chloride were dissolved in a portion of the water and the pH adjusted to 7.5 + 0.2 using 2.5N hydrochloric acid. Tiloxapol and polyhexamethylene biguanide hydrogen chloride salt were dissolved. The solution was adjusted with purified water to make up. The solution was sterilized through a 0.22 micron filter.

Comparative disinfection results are given in the following table. All tests for a specific microorganism were performed on the same day, thus eliminating inaccuracies sometimes caused by day-to-day variations in the activity of microorganisms from the same source. Differences in logarithmic reductions of less than 0.5 logs are considered to be within experimental error.

Log Reduction (4 hours)

Solution No.

<td>Microoraanism</td><td>3A</td><td>3B</td><td>3C</td>

<td>Pseudomonas aeruginosa (Pa)</td><td> 3,7</td><td> 4,7</td><td> &gt;6,7</td>

<td>Pseudomonas cepacia (Pc)</td><td> 0,2</td><td> 2,2</td><td> 3,2</td>

<td>Miniature Pseudomonas (Pd)</td><td> 1,2</td><td> 5,5</td><td> 5,5</td>

<td>Pseudomonas fluorescens (Pf)</td><td> 0,7</td><td> 4,8</td><td> 5,7</td>

<td>Staphylococcus epidermidis (Se)</td><td> &gt;6,5</td><td> &gt;6,5</td><td> &gt;6,5</td>

<td>Serratia marcescens (Sm)</td><td> 1,8</td><td> &gt;5,5</td><td> &gt;5,5</td>

<td>Candida Albicans (Ca)</td><td> 0,0</td><td> 3,1</td><td> 2,2</td>

<td>Aspergillus fumigatus (Af)</td><td> 0,5</td><td> 0,4</td><td> 0,5</td>

<td>Aspergillus niger (An)</td><td> 0,0</td><td> 0,0</td><td> 0,0</td>

<td>Acinetobacter calcoaceticus (Ac)</td><td> 2,3</td><td> 4,1</td><td> 4,8</td>

<td>Bacillus cereus (Bc)</td><td> 3,8</td><td> 3,9</td><td> 4,1</td>

<td>Bacillus pumilus (Bp)</td><td> 3,0</td><td> 2,9</td><td> 2,9</td>

<td>Cornybacterium xerosis (Cx)</td><td> 4,9</td><td> 2,8</td><td> 2,5</td>

<td>Enterobacter cloacea (Ec)</td><td> 5,8</td><td> 5,9</td><td> 5,5</td>

<td>Enterococcus faecalis (Ef)</td><td> 2,9</td><td> 5,8</td><td> 4,4</td>

<td>Micrococcus luteus (M1)</td><td> 4,8</td><td> 5,0</td><td> 5,4</td>

<td>Proteus mirabilus (Pm)</td><td> 2,9</td><td> 3,1</td><td> 4,3</td>

<td>Candida parapsilosis (Cp)</td><td> 0,3</td><td> 5,0</td><td> 4,3</td>

<td>Fusarium solani (Fs)</td><td> 4,2</td><td> 6,2</td><td> 6,2</td>

Pseudomonas species are very virulent and have major implications for contact lens wear-related eye infections. For the four Pseudomonas species in the previous table, the disinfectant of the present invention was superior for three species and superior to solution 3A but equal to solution 3B for the fourth species.

For the other bacteria and fungi involved in contact lens wear, namely Se, Sm, Ca, Af, Bc, Fs, and Cp, the solution of this invention is equal to or better than 3A or B in five of seven examples and the others. For both Ca and Cp fungal organisms, a significant reduction was observed (greater than 99.4% based on 10 inoculants.

For the other organisms tested that are pathogenic but generally have no eye involvement, the test results revealed substantially the same performance.

Based on the foregoing analysis, it is apparent that the present invention provides novel methods and compositions for contact lens disinfection.

Example 4: Workaround for Cleaning / Disinfecting Contact Lenses

1.2% Tromethamine / Tromethamine Hydrochloride (pH = 7.2)

0.05% Disodium Edetate

0.37% Sodium Chloride

0.01% Tiloxapol ▼ 0.0001% Polyhexamethylene biguanide hydrochloride

qs USP Purified Water

Example 5:

This example illustrates the synergistic antimicrobial effect of the present invention at very low concentrations of peroxide.

<td rowspan="2">1 | Ex.</td><td rowspan="2">Tris % W / v</td><td rowspan="2">DiNa EDTA % W / v</td><td rowspan="2">^H2 ° 2 PPM</td><td colspan="3">i 1 | Log Reduction (4 h) | 1_1</td>

<td>1 | Sm I</td><td>If</td><td>1 ca |</td>

<td>| 5A</td><td> 1,2</td><td> 0,05</td><td> 50</td><td>1 I&gt; 5.8 I</td><td> 5,3</td><td></td>

<td>| 5B</td><td> 1,2</td><td> 0,05</td><td> 50</td><td>1 I&gt; 6.4 1</td><td> —</td><td>&gt; 5.9 | I</td>

<td>| 5C</td><td colspan="2">(Comparative, see</td><td>below)</td><td>1 I 1.5</td><td> 0,8</td><td>J</td>

<td>| 5D 1_</td><td colspan="2">(Comparative, see</td><td>below)</td><td>1 I 1.9 1</td><td> —</td><td> 5,3| _1</td>

The CibaVision Product Solution.

The solution for R saline solution Unisol a

R Example 5C was Software Saline, Example 5D was AOSept diluted with 0.1% h₂O₂