CA2098299C

CA2098299C - Method and composition for disinfecting contact lenses

Info

Publication number: CA2098299C
Application number: CA002098299A
Authority: CA
Inventors: Mary Mowrey-Mckee; Kenneth Bliznik; Ralph Stone
Original assignee: Allergan Inc
Current assignee: Johnson and Johnson Surgical Vision Inc
Priority date: 1990-12-27
Filing date: 1991-12-18
Publication date: 1997-05-20
Anticipated expiration: 2011-12-18
Also published as: EP0564510A1; NO932340D0; US5593637A; EP0766970A2; EP0766970A3; AU9106091A; NO932340L; WO1992011876A1; AU653768B2; RU2067456C1; SG49774A1; MX9102828A; FI932932A; UA26334A; HU9301879D0; IL100487A; BR9107284A; US5422073A; TR25734A; JP2875887B2

Abstract

The present invention covers a method for disinfecting a contact lens comprising contacting the lens with an isotonic aqueous solution comprising 0.6 to 2 weight percent tromethamine (preferably 0.8 to 1.5 percent) for a time sufficient to disinfect the lens. Other aspects include adding to the solution from 0.01 to 1 weight percent chelating agent (preferably disodium EDTA) and/or additional microbicide.

Description

yvo 92/11876 PCrJUS91~0918~
. .

MFTHOD AND COMPOSITION FOR DISINFFCTING
CONTACT LENSES
A disinfectant for soft contact lenses must have, in combination, the following properties:
(1 ) it must perform the required disinfection, ~n~

(2) it must be harmless to soft contact lenses, ~
(3a) any remaining on the lens after disinfection must be harmless to the eye of the contact lens wearer or (3b) it must be capable of being neutralized to a harmless form prior to the wearer's use ot the lens.
Three percent hydrogen peroxide adequately fulfills (1), (2) and (3b).
20 However, the neutralization step is considered undesirable by many users.
Hence, it is far more desirable to have a disinfectant that fulfills (1), (2) and (3a).
International Patent Publication No. WO 91/01763 discloses that solutions having very low concentrations of peroxide, i.e., from 0.01 to 25 0.~ percent more preferably 0.0~ to 0.2 percent can provide disinfection without requiring neutralization. Use of the present invention greatly enhances the microbicidal efficacy of peroxide in such low concentrations.

WO 92/1 1876 PCI`/US91/0918 - 20982~9 U.S. Patent No. 4,7~8,~95 (Ogunbiyi, et al.) discloses that polyhex~n-etl,ylene biguanide (Pl IMB) and its water-soluble salts can fulfill minimal disinfection and be harmless to the eye and the lens, if used with a specific buffer, a surfactant, and in specific concentrations.
The present invention, in its preferred aspccts, has superior disinfection properties and is substantially nonirritating as observed clinically. The present invention is based upon th~ surprising finding that tromethamine and its salts, in proper concentration, is a bactericide and fungicide. Furthermore, tromethamine has a synergistic effect when combined with other known microbicides and chelating agents.
The present invention may be summarized as a method for disinfecting a contact lens comprising contacting the lens with an isotonic aqueous solution comprising 0.6 to 2 weight percent tromethamine (preferably 0.8 to 1.5 percént) for a time sufficient to disinfect She lens. Other aspects include adding to the solution trom 0.01 to 1 weight percent chelating agent (preferably disodium EDTA) and/or additional microbicide, (preferably 0.00001 to 0.1) weight percent PHMB, N alkyl-2-pyrrolidone, chlorhexidine, polyquaternium-1, hexetidine, bronopol, alexidine, low concentrations of peroxide, and ophthalmologically acceptable salts thereof.
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 the solution at its eftective concentration and will not harm the eye or the lens. Examples of ophthalmologically _ 2U98299 acceplable ingredients are given throughout the speci~ic~lion. Of course, use of other ophthalmologically acceptal)le ingredients is within the scope of this invention.
In one aspect of the present invention, there is provided a contact 5 lens disinfecting solution co,~ ising:
(a) 0.6 to 2 weight percenl of a first microbicide comprising tromethamine, its ophthalmologically acceptable salts, or mixtures thereof;
(b) 0.01 to 1 weight percent of an ophthalmologically acceptable chelating agent;
(c) 0.00001 to 0.01 weight percent of a second microbicide selected from the group consisting of PHMB, N-alky1-2-pyrrolidone, chlorhexidine, polyquaternium-1, hexetidine, bronopol, alexidine, from 50 to 200 ppm hydrogen peroxide, ophthalmologically acceptable salts thereof, and mixtures thereof;
(d) 0.01 to 0.5 weight percent sodium chloride;
(e) acid q.s. ad acceplable ocular pH; and (f) water q.s. ad 100 percent.
In another aspect of the present invention, there is provided a contact lens disinfecting solution comprising:
(a) 0.6 to 2 weight percent of tromethamine;
(b) 0.01 to 1 weight percent of disodium EDTA;
(c) 0.00001 to 0.1 weight percent of a component selected from the group co,lsi~ling of PHMB, ophthalmologically acceptable salts thereof and mixtures thereof;
(d) 0.005 to 5.0 weight percent of tyloxapol;
(e) sodium chloride in an amount effective to render said contact lens disinfecting solution isotonic; and .. .. . .. . . .

20982~
-3a-(f) water q.s. 100 percent, said contact lens disinfecting solution having an ocularly compatible pH.
The present invention has the advantage of providing a method and a composition for disinfecting contact lenses for a wide range of 5 microorganisms such as Fusarium solani, Aspergillus fumigatus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Serratia marcescens, Candida albicans, and Herpes simplex. Of these, disinfecting of S.
marcescens and C. albicans on lenses has proven particularly difficult with prior art compositions. The present invention also has the advantage of providing a 10 method and a composition for disinfecting contact lenses which is compatible with, and has little or no undesirable chemical reactions with hydrophillic contact lenses. Another advantage of the present invention is that it provides amethod and a composition for disinfecting contact lenses which has a low pote"lial for irritating the eyes. And still yet another advantage of the present 15 invention is that in certain embodiments, it provides a method and composition for disinfecting contact lenses, for cleaning tear film debris from conlact lenses, and for lubricating contact lenses.
Tromethamine, whose chemical name is 2-amino-2-hydroxymethyl-1,3-propanediol, is also known by the names of trimethylol 20 aminomethane; tris(hydroxymethyl)aminomethane; trisamine; tris buffer;
trometamol; Tromethane; THAM; TRIS; Talatrol; Tris Amino; Tris-steril; Trizma as described in the Merck Index, Eleventh Edition, Published by WO 92/11876 PCr/USs1/os18s Merck & Co., Inc. Rahway, N.J. (1989). Tromethamine and its salts act as buffers over the pH range of 6-9. In the ANGUS Chemical CG.IIPanY
Technical Bulletin TB 69, TRIS AMINO~9 as a buffer for pH control, Angus Chemical Company it is ~isclQsed that TRIS AMINO holds the pH of contact 5 lens cleaning solutions in thc range most favorable tor hydrolysis of protein films on lens surfaces, and that the lack of eye irritancy of TRIS AMINO are of prime consideration in its choice tor this application. However the ANGUS technical bulletin fails to disclose use of tromethamine in formutating contact lens disinfecting solutions, the fact that tromethamine 10 has microbicidal properties, nor the fact that tromethamine has a synergistic effect when combined 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, nitrilo 15 triacetic acid, diethylene triamine pentaacetic acid, hydroxyethyl ethylenediamine triacetic acid, 1,2-diaminocyclohexane tctraacetic acid, ethylene glycol bis (beta-aminoethyl ether) in N, N, N', N' tetraacetic acid (EGTA), amino diacetic acid and hydroxyethyl amino diacetic acid. These acids can be used in the forrn of their water soluble satts, particularly their alkal; metal 20 salts. Especially preterred chelating agents are the di-, tri- and tetra-sodium satts of ethylene diamine tetraacetic acid (EDTA), most preferab!y disodium EDTA (Disodium Edetate).
Other chelating agents such as citrates and polyphosphates can also be used in the present invention. The citrates which can be used in the WO 92/11876 - PCr/US91/0918~

-2nss2qs present invention include citric acid and its mono-, di-, and tri-alkaline metalsalts. The polyphosphates which can be used include pyrophosphates, triphosphtes, tetraphosphates, tri~"alaphosphales, tetrametaphosphates, as well as more highly condensed phosphates in the form ot the neutral or 5 acidic alkali metal salts such as the sodium and potassium salts as well as the ammonium salt.
The pH of the solutions should be ~djl sted to be compatible with the eye and the contact lens, such as between 6.0 to 8.0, preferably between 6.8 to 7.8. Significant deviations from neutral (pH = 7) will cause 10 changes in the physical parameters (ie. diameter) in some contact lenses.
Low pH (pH less than ~.5) can cause burning and stinging of the eyes, while very low or very high pH (less than 3.0 or greater than 10) can cause ocular damage.
The terrn ~disinfect~ means the rendering non-viable ot 15 substantially all pathogenic microbes that are in the vegetative state, including gram negative and gram positive bacteria, as well as tungi.
The additional microbicides employed in the present invention are known, such as polyhexamethylene biguanide, N-alkyl-2-pyrrolidone, chlorhexidine, polyhexamethylenebiguanide, alexidine, polyquaternium-1, 20 hexetidine, bronopol and a very low concentration of hydrogen peroxide, e.g., 50 to 200 ppm.
- The solutions of the invention are compatible with both rigid gas permeable and hydrophilic contact lenses during cleaning, wetting, soaking, rinsing and disinfection.

WO 92/11876 PCI`/US91/0918~

~- 20q8299 One embodiment of the invention is a combination of dry, solid, water solublo or dispersible unit ~Josa!Ja forms, eg. tablets. One type of tablet would contain the tromethamine or salt thereof, the microbicide, and the chelating agent. Prior to use, the tablet is dissolved in the diluent, eg. water or saline to form a solution for disinfe~ting contact lenses.
Another embodiment would be an aqueous solution comprising the novel disinfecting ingredients.
-A typical aqueous solution of the present invention may contain additional ingredients which would not affect the basic and novel 10 characteristics of the active ingredients described earlier, such as tonicityagents, surfactants and viscosity inducing agents, which may aid in either the lens cleaning or in providing lubrication to the eye. Suitable tonicity agents include sodium chloride, potassium chloride, glycerol or mixtures thereot. The tonicity ot the solution is typically ~justed to approximately 15240-310 milliosmoles per kilogram solution (mOsm/kg) to render the solution compatible with ocular tissue and with hydrophilic contact lenses.
Suitable surfactants include tyloxapol, which is 4-(1,1,3,3-tetramethylbutyl)phenol polymer with formaldehyde and oxirane; pluronic~
or poloxamers, nonionic block copolymer surfactants which are block 20 copolymers of propylene oxide and ethylene oxide; octoxynol or octyphenoxy polyethoxyethanol prepared by reacting isooctylphenol with ethylene oxide; poloxarnine which is a block copolymer derivative of ethylene oxide and propylene oxide combined with ethylene diamine; and nonoxynol nonicnic surfactant mixtures prepared by reacting nonylphenols WO 92/11876 - PCI-/USgl/0918~

with ethylene oxide. Most of these surfactants are described in the Merck - Index, supra. The SIJ~ 18.,1ant5 can be employed 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 trom about 0.025 to about 1 psrcent by 5 weight.
Suitable viscosity inducing agents can include lecithin or the cellulose derivatives such as hydroxyn,ell.~rlcellulose, hydroxypropylcellulose and methylcellulose in amounts similar to those for surfactants, above.
If solid dosage torms 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 varying between 0.001 and 30 % by weight, preferably between about 0.1 and 5 percent.
1~ The preferred aqueous solutions of the invention can be prepared by adding the ingredient as follows. Add the tromethamine to water. Adjust the pH of the solution to a pH from about 6.8 to about 7.8.
Add the chslating agent and the tonicity agent, if required. Stir to dissolve the above ingredients. Optionally, add the surfactant and the viscosity 20 inducing agent. Add the microbicide. The final produ t can be rendered sterile by sterile filtration, heat sterilization or a combination thersof.
A suggested method for disinfecting a contact lens is as follows. The lenses are first rubbed with a few drops of the subject solution or saline and rinsed to remove surface contaminants such as mucous, eye WO92/11876 PCI/US91/0918~

20982q9 makeup, etc., and then placed in a suitable container with a sufficient amount ot the s'~ J9C!JS solution to cover the lenses. The lenses are allowed to soak for at least 10 minutes and up to 8 hours to achieve subst~ntial kill of the microor~anisms. The foregoing method is carried out at ambient or at elevated temperatures, ie. 20C to about 1 00C.
To illustrate the manner in which the invention may be carried out, the following examples are given. It is ul~J6latOOd, however, that the - examples are for the purposes of illustration and the invention is not to be regarded as limited to any of the specific materials or conditions set forth 10 therein. The term ~q.s.~ means quantum sufficiat or ~a sufficient volume~--tobring the aqueous solution to volume. Unless otherwise stated, ~%" means weight per unit volume expressed as a percent ~(w/v).~
The disinfecting efficacy was determined by inoculating the test solution with a microbial suspension at a final concentration of 1 5 approximately 1 o6 colony forrning units per ml. Each inoculated solution was then vigorously agitated and kept at ambient temperature.
At various times after inoculation each solution was vigorously agitated and one ml. aliquots withdrawn and dispensed-into 9 ml of neutralizing broth. Ten-fold serial dilutions ot each inoculated solution were 20 prepared in neutralizing broth. The solutions were plated out at effective dilutions of 1/10th to 1/100,QOOth on nutrient agar with or without neutralizing agents. The plates were incubated under optimal conditions of time and temperature for growth and the colonies counted.

WO 92/11876 PCI/US91/0918~

--The concentration of the survivors and the log reductions were c~l~J'~te~ Each ten-told clecn3ase in conce,ltralion constitutes a one-log reduction.
FX~nU?Ie 1 This example illustrates the surprising efficacy of tromethamine in an isotonic aqueous solution as a microbicide that is effective against difficult-to-WII organisms.

Fx~n~le 1A: Isotonic aqueous solution containing tromethamine.

Tromethamine 1.2%
Sodium Chloride 0.3%
HCI q.s.adpHof7.4 Puritied Water USP q.s. ad 100 ml.

FY:~mple 1 R Isotonic solution containing tromethamine and chelating agent.

Tromethamine 1.2%
Sodium Chloride 0.3%
Disodium EDTA 0.05%
HCI q.s. ad pH of 7.4 Purified Water USP q.s. ad 100 ml.
Both tromethamine solutions ar~ prepared by dissolving the ingredients in water, adjusting the pH with hydrochloric acid and bringing to volume with additional water. Each solution is sterilized using a 0.22 micron filter.

WO 92/11876 ` PCI-/US91/0918~

r - 1 0 - - 2 () 9 8 2 9 9 F~am~le 1 C (Com~arative): Isotonic borate solution.

Boric Acid t .03%
Sodium Borate 0.19%
Sodium Chloride 0.3%
Purified Water USP q.s. ad 100 ml.

Fx~m~le 1 n (com~r~tive): Isotonic borate solution and chelating agent.

Boric Acid 1.03%
Sodium Borate 0.19%
Sodium Chloride 0.3%
Disodium EDTA 0.05%
Purified Water USP q.s. ad 100 ml.

Both borate solutions are prepared by dissolving the ingredients in water and bringing to volume with additional watsr. The pH of the solution is 7.4.
10 Each solution is stsrilized by filtering through a .22 micron filter.

Fx~m~le ~F (Com~r~tive): Isotonic phosphate solution.

Sodium Dihydrogen 0.16%
Phosphate Disodium Hydrogen 0.757%
Phosphate Sodium Chloride 0.44%
Purified Watsr USP q.s. ad 100 ml.

WO 92/11876 PCr/US91/0918~

`' P 11. 20q829~

FY~rn~le ~F (Com~r~tivs): Isotonic phosphate solution and chelating a~ent.

Sodium Dihydrogen 0.16%
Phosphate Disodium Hydrogen 0.757%
Phosphate Sodium Chloride 0.44%
Disodium EDTA 0.05%
Purified Water USP q.s. ad 100 ml.

Both phosphate solutions were prepared by dissolving the ingredients in wat~r and adjusting to volums with additional water. The pH of the solution is 7.4. The formulation for the phosphato solution without chelator is identical to that listed in the USP tor isotonic ophthalmic saline. The solutions were sterilized by filtering through a 0.22 micron filter.
o When tosted tor disinfectin~ 6~ficacy, the following results were achieved:

I n~ Rerlllction ::lt F ollr Hol~rS

Fx~m~le S. m~rcescens C. ~Ibicans 1A (This invention) 2.6 1 4 1B (This invention) 4.9 1.9 1C (Comparative) 0.~ <0.1 1D (Comparative) 0.7 cO
1E (Comparative) 0.8 <0.1 1F (Comparative) 0.7 ~0.1 1~
- As can be seen, isotonic aqueous solutions containing 1.2%
tromethamine reduced the concentrations of two difficult-to-kil! organisms WO g2/11876 ! PCr/US91/Osl8~

- ~ - 12- 2098299 by a factor of greater than 10. Furthermors, tromethamine has a synergistic effect when combined with a chelating agent, disodium EDTA. In contrast, isotonic ~ eous solutions containing borate and phosphate buffer systems, with or without disodium EDTA, have significantly less disinfection 5 efficacy.

WO 92/11876 Pcr/usgl/ogt8~i ~_ -13- 20q8299 I -- . . . . . . O
~ Q
-.o C' lL : ~ o ~ ' ._ ._ s ~ ~ ~ :
x Q

C o ~ ~ _ .~ ~
u~ ID
o C~ ~ o O_ c E
E o :~
~L o E 5 u~

~ o Q
- o ~n ~ m o I Q
P ~ _ o ~

UJ~ ooOOOOOO--C ~ o o o o o o o o o -- C~
c Q
C
o~ ~
J N 1~1 N N N N
O O _ ,_ _ _ _, E-o E
C~ .
X z ~ D N C~l N N C~J NN

C X

WO 92/11876 PCl-/US91109185 _ ~ - 14- 2098299 In the above table: -DiNaEDTA is disodium EDTA.
PHMB is polyhexamethylene biguanide hydrochloride salt, a microbicide.
S Onamer MIM, PolybrenerM, and Hexetidine~M, are microbicides.
CG is chlorhexidine gluconate, a microbicids AH is alexidine hydrochloride, a microbicide Tyloxa~ol is a surfactant.
In addition to the above-listed ingredients, each solution contained 0.37% Na Cl for isotonicity and the pH of each solution was adjusted to 7.4 with HCI.
Following are log reductions for various organisms after 4 hours.

Ex. No. S.m. S.e. C.a. A.n. A.f.
2a 5.4 >5.3 -- -- --2b 2.3 3.6 -- -- --2c ~6.8 - -- -- 1.1 2d >6.8 -- -- -- 1.3 2e -- ~ -- -- 1.6 2f -- -- -- 1 . 3 29 -- >5.7 2.0 --2 h -- ~ >5.7 1 .2 - --2i >6.1 -- 1.1 -- --S.m is Serratia marcescens S.e. is Staphylococcus epidermidis C.a. is Candida albicans A.n. is Aspergillus niger A.f. is Aspergillus fumigatus WO 92/11876 PCr/US91/0918~

~ 15- 2098299 Fx~rnple 3 This example co"~pares the disinfeclion ability of a preferred formulation of this invention prepared in a manner suitable tor making 5 commercial quantities. with two commercial solutions.

Sollltion 3A
A commercial solution tradenamed Optifree; described in its package insert as a stenile, buffered, isotonic, aqueous solution containing 10 a citrate b~ffer and sodium chlonde with edetate disodium 0.05% and POLYQUAD2 (polyquaternium-1 ) 0.001% as preservatives."
Solution 3B
A commercial solution tradenamed ReNu~9 Multi-Purpose 5 Solution described in its package insert as ~A sterile, isotonic solution thatcontaines boric acid, poloxamine, sodium borate, and sodium chloride;
preserved with DYMEDrM (polyaminopropyl biguanide) 0.00005% and edetate disodium 0.1%.
20 Solution 3C (This invention) Tromethamine 1.2 %
Disodium edetate 0.05 %
NaCI 037 %
Tyloxapol 0.025%
Polyhexamethylene biguanide, HCI salt 0.0001%
Hydrochloric acid adjust to pH 7.5 + 0.2 USP Purified Water q.s. ad 100%
Tromethamine, disodium edetate and sodium chloride were dissolved in a portion of the water and the pH was adjusted to 7.5 + 0.2 25 using 2.5N Hydrochloric acid. Tyloxapol and polyhexamethylene Wo 92/11876 Pcr/US91/o918~

_, - 16- 20982q9 biguanide hydro~en chloride salt were added and allowed to dissolve. The solution was ~djusted to volume with pufifi~d water. The solution was sterilized through a 0.22 micron sterilizin~ filter.
Comparative disinfec~ion results are given in the following 5 table. All tests for a particular microorganism were performed on the same day, thereby eliminating the inaccuracies sometimes caused by day-to-day variations in the activity of microorganisms trom the same source.
Differences in lo~ reductions of less than 0.5 logs are considered to be within experimental error.
l oo Reduction (4 hours) Microor~nism .Ciollltion No.
;~ 3B ;~
Pseudomonas aeruginosa (Pa) 3.7 4.7 '6.7 Pseudomonas cepacia (Pc) 0.2 2.2 3.2 Pseudomonas diminuta (Pd) 1.2 5.5 5.5 Pseudomonasfluorescens (Pf) 0.7 4.8 5.7 Staphylococcus epidermidis (Se) 2 6.5 2 6.5 > 6.5 Serratia marcescens (Sm) 1.8 2 5.5 > 5.5 Candida albicans (Ca) 0.0 3.1 2.2 Aspergillus fumigatus (Af) 0.5 0.4 0.5 Aspergillus niger (An) 0.0 0.0 0.0 Acinetobacter calcoaceticus (Ac) 2.3 4.1 4.8 Bacillus cereus (~c) 3.8 3.9 4.1 Bacillus pumilus (Bp) 3.n 2.9 2.9 Cornybacterium xerosis (Cx) 4.9 2.8 2.5 Enterobacter cloacea (Ec) 5.8 5.9 5.5 Enterococcus faecalis (Ef) 2.9 5.8 4.4 Micrococclus luteus (Ml) 4.8 5.0 5.4 Proteus mirabilus (Pm) 2.9 3.1 4.3 Candida parapsilosis (Cp) 0.3 5.0 4.3 Fusarium solani (Fs) 4.2 6.2 6.2 WO 92/11876 Pcrl us9~ 8~

- 17- 20q829q Pseudomonas SpQcies are ve~y virulent and are highly implicated in ocular intections relatsd to CG~ ~ lens wear. For the four Pseudomonas species in the above table, the disinfectant of the present 5 invention was superior for three species and superior to solution 3A, but equal to solution 3B, tor the tourth species.
For other bacteria and fungi implicated in contact lens wear such as Se, Srn, Ca, Af, Bc, Fs, and Cp, the solution of this invention is equal to or better than 3A or B in five of the seven examples and in the other 10 two fungal organisms Ca and Cp, significant reduction (greater than 99.4%
based on a 1 o6 inoculùm) was observed.
For the other organisms tested which are pathogens but not ~enerally implicated in the eye, the test results demonstrated substantially equal performance.
1 5 Based on the above analysis, it is clear that the present invention provides inventive methods and compositions for disinfecting contact lenses.

F~m~le 4. Alternative contact lens cleaning/disinfecting solution 1.2% Tromethamine/Tromethamine Hydrochloride (pH=7.2) 0.05% Disodium Edetate 0.37% Sodium Chloride 0.01 % Tyloxapol 0.0001% Polyhexamethylene Biguanide, hydrochloride q.s. Purified water, U.S.P.

WO 92/11876 PCI/US91/0918~

`

Fx~ C le S
This example illustrates the synergistic anti-microbial effect of the present invention for very low concentrations of peroxide.

TrisOi Na EDTA H22 Log Reduction '4Hr) Ex. No. %WN %WN PPM Sm Se Ca 5A 1.2 0.05 50 ~5.8 5.3 5B 1.2 0.05 50 ~6.4 - ~5.9 5C (Comparative, see below) 1.5 0.8 --5D (Comparative. see below) 1.9 -- 5.3 The solution for example 5C was Software Saline~9 a CibaVision product.
The solution for example 5D was AOSept~ diluted with 10 Unisol~ saline to 0.1% H2O2.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A method for disinfecting a contact lens comprising contacting the lens with an isotonic aqueous solution comprising 0.6 to 2 weight percent tromethamine or its ophthalmologically acceptable salts for a time sufficient todisinfect the lens.

2. The method of claim 1 wherein the solution comprises 0.8 to 1.5 weight percent tromethamine or its salts.

3. The method of claim 1 or claim 2 wherein the disinfection reduces the concentration of microorganisms selected from S. marcescens, C. albicans, or both.

4. The method of claim 1 wherein the solution further comprises from 0.01 to 1 weight percent of an ophthalmologically acceptable chelating agent.

5. The method of claim 4 wherein the chelating agent is disodium EDTA.

6. The method of claim 1 wherein the solution includes an additional microbicide comprising 0.00001 to 0.01 weight percent of a microbicide selected from PHMB, N-alkyl-2-pyrrolidone, chlorhexidine, polyquaternium-1, hexetidine, bronopol, alexidine, very low concentration of peroxide, ophthalmologically acceptable salts thereof and mixtures thereof.

7. The method of claim 6 wherein the additional microbicide is PHMB, ophthalmologically acceptable salts, or mixtures thereof.

8. A contact lens disinfecting solution comprising:
(a 0.6 to 2 weight percent of a first microbicide comprising tromethamine, its ophthalmologically acceptable salts, or mixtures thereof;
(b)0.01 to 1 weight percent of an ophthalmologically acceptable chelating agent;
(c)0.00001 to 0.01 weight percent of a second microbicide selected from the group consisting of PHMB, N-alkyl-2-pyrrolidone, chlorhexidine, polyquaternium-1, hexetidine, bronopol, alexidine, from 50 to 200 ppm hydrogen peroxide, ophthalmologically acceptable salts thereof, and mixtures thereof;
(d) 0.01 to 0.5 weight percent sodium chloride;
(e) acid q.s. ad acceptable ocular pH; and (f) water q.s. ad 100 percent.

9. The contact lens disinfecting solution of claim 8 comprising:
(a) 1.2 weight percent of said first microbicide;
(b) 0.05 weight percent of said ophthalmologically acceptable chelating agent;
(c) 1 ppm of said second microbicide;
(d) HC1 q.s. ad pH of 7.3 to 7.7;
(e) 0.0001 to 20 weight percent of a surfactant;
(f) 0.37 weight percent sodium chloride; and (g) water q.s. ad 100 percent.

10. The contact lens disinfecting solution of claim 8 or 9 wherein said ophthalmologically acceptable chelating agent comprises disodium EDTA.

11. The contact lens disinfecting solution of claim 9 wherein said second microbicide comprises PHMB, ophthalmologically acceptable salt thereof, or mixtures thereof.

12. The contact lens disinfecting solution of claim 10 wherein said surfactant comprises 250 ppm of tyloxapol.

13. The method of claim 2 wherein the solution further comprises from 0.01 to 1 weight percent of an ophthalmologically acceptable chelating agent.

14. The method of claim 3 wherein the solution further comprises from 0.01 to 1 weight percent of an ophthalmologically acceptable chelating agent.

15. The contact lens disinfecting solution of claim 8 wherein said firstmicrobicide is present in an amount of 0.8 to 2 weight percent.

16. The contact lens disinfecting solution of claim 8 wherein said second microbicide is selected from the group consisting of PHMB, ophthalmologically acceptable salts thereof, and mixtures thereof.

17. The contact lens disinfecting solution of claim 10 wherein said second microbicide is selected from the group consisting of PHMB, ophthalmologically acceptable salts thereof, and mixtures thereof.

18. A contact lens disinfecting solution comprising:
(a) 0.6 to 2 weight percent of tromethamine;
(b) 0.01 to 1 weight percent of disodium EDTA;

(c) 0.00001 to 0.1 weight percent of a component selected from the group consisting of PHMB, ophthalmologically acceptable salts thereof and mixtures thereof;
(d) 0.005 to 5.0 weight percent of tyloxapol;
(e) sodium chloride in an amount effective to render said contact lens disinfecting solution isotonic; and (f) water q.s. 100 percent, said contact lens disinfecting solution having an ocularly compatible pH.

19. The contact lens disinfecting solution of claim 18 having a pH
between 6.8 and 7.8.

20. The contact lens disinfecting solution of claim 18 which contains 1.2 weight percent tromethamine, 0.05 weight percent disodium EDTA, 0.0001 weight percent component (c) and 0.025 weight percent tyloxapol.