AU730031B2 - Polymer, article and method for inhibiting the growth of ocular pathogens in eye care products - Google Patents

Description

Our Ref: 730655 P/00/011 Regulation 3:2

AUSTRALIA

Patents Act 1990

ORIGINAL

COMPLETE SPECIFICATION STANDARD PATENT a a Applicant(s): Address for Service: Invention Title: Allergan Sales, Inc 2525 Dupont Drive, Irvine, California, 92612 UNITED STATES OF AMERICA DAVIES COLLISON CAVE Patent Trade Mark Attorneys Level 10, 10 Barrack Street SYDNEY NSW 2000 Polymer, article and method for inhibiting the growth of ocular pathogens in eye care products The following statement is a full description of this invention, including the best method of performing it known to me:- 5020 POLYMER, ARTICLE AND MEHOD FOR INHIBrNG THE GROWTH OF OCULAR PATHOGENS IN EYE CARE PRODUC73 Field of the Invention The present invention relates to the inhibition of the growth of ocular S pathogens, particularly protozoa, in eye care products such as ophthalmic solutions and on the surfaces of eye care products such as contact lenses. More specifically, the present invention relates to a polymer useful in inhibiting the growth of protozoa and other ocular pathogens, an article comprising the 10 polymer, and a method employing such an article. oooo Background of the Invention Eye care products, such as contact lens care systems, are susceptible to contamination by ocular pathogens. Known ocular pathogens include bacteria, fungi, and also protozoans such as amoebae, for example the acanthamoebae.

Acanthamoebae are ubiquitous free-living protozoans, which exist in two distinct morphological forms: the trophozoite and the cyst. The trophozoite form is the free swimming form and is relatively easy to kill. The organism encysts in an adverse environment, creating a thick protective coat making it very difficult to kill. The cyst form is the hibernating form of the organism.

The organism reverts to the trophozoite form in a favorable environment.

A variety of species of Acanthamoeba have been found to cause infectious keratitis. These species include A. polyphaga, A. castellanii, A. lenticulata,

A.

hatchetti, A. astronyxis, A. culbertsoni, A. rhysodes, and others. See, for example, Ma et al., Rev. Infectious Diseases 1990 May/June; 12(3):490-513 and the references cited therein. Moreover, acanthamoebae use bacteria and fungi as a food source. Co-contamination of contact lens care system with bacteria and fungi facilitates the growth of the acanthamoebae in the contact lens care system, and is thus implicated as a risk factor for acanthamoebic keratitis.

The incidence of ulcerative keratitis among soft contact lens wearers in the United States has been found to be a function of contact lens wear mode. An incidence of infection of 4.1 per 10,000 daily wear patients per year and 20.9 per 10,000 extended wear patients per year has been found. Thus of the approximately 20 milion contact lens wearers in the United States, over 12,000 infections (from all causes) occur yearly. Acanthaxnoebjc keratitis has been reported in contact lens wearers regardless of lens type.

Various agents have been found to be effective in killing and/or inhibiting the growth of bacteria or fungi. For example, U.S. Patent No. 4,499,077 to Stockel discloses an antimicrobial composition for soft contact lenses including an oxidizing agent such as an- oxyhalogen compound, stabilized chlorine dioxide or hydrogen peroxide, and a polymeric germnicide, a quaternary ammnonium polymer or an amino and/or imino polymer or salts thereof.

U.S.

Patent No. 4,654,208 to Stockel discloses an antimicrobial composition for contact lenses including an aqueous solution of a germicidal polymeric nitrogen :compound and an oxidizing agent, chlorine dioxide, chlorite, stabilized chlorine dioxide or hydrogen peroxide, to potentiate the activity of the 15 germicidal polymeric nitrogen compound at low concentrations. However, no agents have been proposed as effective in inhibiting the- growth of protozomns.

In U.S. Patent No. 5,382,599, to Rupp et at.' it is disclosed that various polyvalent cation chelating agents, such as EDTA, are effective per se in inhibiting the growth of protozoans, including amoebae such as acanthamoebac.

An effective protozoan-growth inhibiting amount of a chelating agent is added directly to an eye care product such as a contact lens care solution.

It would be desirable to provide additional methods and compositions for inhibit the growth of protozoans such as acanthamoebae in or on eye care products such as contact lenses, contact lens solutions and contact lens cases, in order to reduce the incidence of acanthamoebic keraitis and other ophthalmic pathologies due to the presence of protozoans.

It would also be desirable to provide methods and compositions that are effective in inhibiting the growth of other ocular pathog:ens, such as bacteria or fungi, as well as protozoans.

Summary of the Preferred Embodiments In accordance with one aspect of the present invention, a polyvalent cation chelating polymer capable of inhibiting the growth of ocular pathogens, in particular protoza, is provided. The polymer has incorporated therein an effective growth inhibiting amount, preferably about 1 to 100 wt%, of a monomer unit containing at least one moiety capable of chelating a polyvalent cation. Very preferably the moiety capable of chelating a polyvalent cation is an -N(CH 2

CO

2

A)

2 group or an

-N(CH

2

CO

2

A)

3 CI group wherein A is hydrogen or an alkali metal cation.

In accordance with an aspect of the present invention, methods of producing a composition of matter capable of chelating a polyvalent cation are provided. One more specific embodiment provides a method which comprises the step of reacting a compound of the formula (IV).

CRsR 6

-CR

7

-(CR

8

R

9 2

CO

2 A)]Cly (IV) 0 15 wherein R,

R

6

R

7

R

8

R

9 independently are H or a Ci-6 alkyl group, /n is an integer from 0 to 18, A is H or an alkali metal cation, 20 x is 2 or 3, and y is 0 or 1, with the proviso that when x is 2, y is 0 and when x is 3, y is 1.

with a composition of matter capable of reacting with an epoxide.

One particularly preferred method employs as the composition of matter capable of reacting with an epoxide a plasma treated solid polymer having surface free radicals.

This preferred method comprises the steps of exposing the solid polymer to a solution or a low pressure vapor comprising the compound having formula (IV) to form a derivatized solid polymer, and neutralizing residual surface free radicals on the derivatized solid polymer by exposing the solid polymer to liquid water or water vapor at low pressure.

Another particularly preferred method employs as the composition of matter capable of reacting with an epoxide a compound of the formula (V)

(V)

CR'R

2 C CO2-R 4 wherein R R 3 independently are H or a CI- 6 alkyl group, and

R

4 is H or a C.- 6 hydroxyalkyl group.

It is particularly preferred to react the compound of formula (IV) with the compound of formula to form a compound of formula (III) as described below.

Another more specific embodiment of a method of producing a composition of S*"0 matter capable of chelatirig a polyvalent cation comprises the step of polymerizing a compound of formula (III) as described below. Optionally, the compound of formula oooo 15 (III) can be copolymerized with one or more additional ehtylenically unsaturated monomers.

In another embodiment, the inventive polymer comprises a plurality of monomer units having the formula (I)

R

3 20

-(CRR

2

CO

2

-R-.CR

5

R-CR

7

-(CR

8

'R

9

)-N[(CH

2 COA)x]Cl (I)

OH

wherein

R

2

R

3 independently are H or a Ci-4 alkyl group,

R

4 is a single bond or a Cis alkylene oxy group,

R

s

R

6

R

7

R

8

R

9 independently are H or a CI -6alkyl group, n is an integer from 0 to 18, A is H or an alkali metal cation, x is 2 or 3, and y is 0 or 1 with the proviso that when x is 2, y is 0 and when x is 3, y is 1.

The polymer can include one or more comonomeric units obtained from ethylenically unsaturated comonomers, in particular hydrophilic comonomers such as alkyl or hydroxyalkyl (alk)acrylates. Preferred comonomeric units have the formula (II)

R

3

-(CR'R

2

I

CO2-R 4 (l) wherein R, R 3 independently are H or a Ci.

6 alkyl group, 15 R' is H or a C hydroxyalkyl group.

In accordance with another aspect of the present invention, there is provided an eye care product, such as a lens case, a container for an ophthalmic solution, or a contact lens, which comprises a polymer as 20 described above.

9 In accordance with a further aspect of the present invention, a compound is provided having the formula (MI)

CR'R

2

=C

CO

2 -xtRRR 6

CR(CRR

9 )ftN[(CH 2

CO

2 A)j]C (Il

O

wherein

R

1

R

2

W

3 independently are H or a alkyl group, K R" is a single bond or a C, 4 alkylene oxy group,

R

5 R6 W, R' independently are H or a alkyl group, n is an integer from 0. to 18, A is H or an alkali metal cation x is 2 or 3, and y is 0or 1 with the proviso that 'when x is 2, y isO0 and when x is 3, y is 1.

The compound is particularly suitable for polymerization to *.:produce a polymer capable of chelating a polyvalent cation.

Compositions of matter produced according to the foregoing methods, and eye care products comprising the inventive polymers and compositions of matter, are also provided, as are methods of inhibiting the growth of ocular pathogens, particularly protozoa, using the inventive eye care products.

Other objects, features and advantages of the present invention will become apparent to those skilled in the art from the following detailed description. It is to be understood, however, that thedetailed description and specific examples, while indicating preferred embodiments of the present invention, are given by way of illustration and not limitation. Many changes and modifications within the scope of the present invention may be made without departing from the spirit thereof, and the invention includes all such modifications.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step.or group of integers or steps.

S* The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that that prior art forms part of the common general knowledge in Australia.

oo~ oooo ooooo 8 Detailed Descrivtion of the Preferred Embodiments U.S. Patent No. 5,382,599, to Rupp et al., the disclosure of which is incorporated in its entirety herein by reference, describes methods and compositions for inhibiting the growth of protozoa in or on the surface of an eye care product. According to Rupp et al, the growth of protozoa is inhibited by contacting the eye care product with an effective protozoan growth-inhibiting amount of a polyvalent cation chelating agent, such as EDTA. The polyvalent cation chelating agent is typically added to an eye care solution to inhibit protozoan growth therein, or to inhibit protozoan growth on the surface of an eye care product with which the solution is in contact.

It has now been discovered that polymers and related compositions of matter can be produced which include a plurality of moieties which are capable of chelating polyvalent cations. The inventive materials thus are also capable of ":'";inhibiting the growth of protozoa.

15 As used herein, a "polyvalent cation chelating polymer" is a polymer which includes at least one moiety that is capable of forming coordination bonds with a cation having a positive charge of at least 2. Such cations include, for S example, Ca 2 Mg 2 Fe 2 Fe 1 Mn+, Zn 2 Cu2+ and Ni'. Polymers including combinations of two or more such moieties are also included within 20 the scope of this term.

In protozoan cells, pahicularly acanthamoeba cells, polyvalent cations such as calcium, magnesium, iron, manganese, and zinc serve as cofactors of enzymes required for metabolism. These polyvalent cations also affect the function and structure of the trophozoite by influencing the tonicity of the environment. Calcium and magnesium have been shown in the literature to be essential for acanthamoeba encystment. See Neff et al., "Induction of Synchronous Encystment (Differentiation) in Acanthamoeba Methods in Cell Physiology, vol. 1, ch. 4, pp. 55-83 Prescott, ed., Academic Press, New York 1977). Calcium salts have also been shown to affect acanthamoeba ameboid locomotion and attachment.

Applicants have thus found that the use of polymers that include polyvalent cation chelating moieties effectively inhibits protozoan cell functions, particularly cell growth, which require such cations.

As used herein, a polyvalent cation chelating polymer "effectively inhibits" protozoan growth if exposure of a solution including a known initial number of protozoa to the polymer over a period of at least seven days results in a constant or reduced number of protozoa. Inhibition of protozoan growth includes in particular prevention of excystment of the protozoa.

The invention is effective in inhibiting the growth of protozoans including, but not limited to, acanthamoebae, for example A. polyphaga, A. castellani,

A.

lnticulata, A. hatchetti, A. astronyxis, A. culbertsoni, and A. rhysodes. The invention is also effective in inhibiting the growth of other protozoans, such as amoebae of the genus Naegleria.

Many other ocular pathogens besides protozoa require one or more of the foregoing polyvalent cations for growth. See, Griffin, Fungal Physiology (John Wiley Sons, Inc. 1981), p. 138 (essential mineral nutrients 15 of fungi); Gottschalk, Bacterial Metabolism (Springer-Verlag New York, Inc. 1979, 1986) pp. 1-3 (minerals essential for bacterial nutrition). Thus, the inventive compositions of matter can inhibit the growth of harmful bacteria and fungi as well as protozoans. -Exemplary ocular pathogens whose growth can be S inhibited by recourse to the present invention include P. aeruginosa, C.

20 albicans and S. marcescens.

The present inventiot provides compositions of matter that can be used in the manufacture of contact lenses, contact lens cases, ophthalmic and lens treatment solution containers, and other products.

The compositions of matter capable of chelating a polyvalent cation according to the instant invention may broadly be characterized as solid or hydrogel polymeric materials. The inventive polymeric materials can be prepared in a number of ways. A monomer including a polyvalent cation chelating moiety can be synthesized and subsequently polymerized, optionally together with one or more comonomers, to produce a polymer incorporating the chelating moiety. Alternatively, a polymeric material not including a polyvalent cation chelating moiety can be chemically modified to incorporate such moieties at least on its surface. For example, an article comprised of a polymeric material can be exposed to a plasma discharge which results in the formulation of free radicals on the surface of the material. The treated surface can then be contacted with an agent including a chelating moiety to produce a derivatized surface capable of chelating polyvalent cations.

In one preferred embodiment, a polymer is provided which comprises an effective growth inhibiting amount, preferably a protozoan growth inhibiting amount, of at least one moiety capable of chelating a polyvalent cation. Preferably, the polymer includes about 1 to 100 wt%, based on the weight of the polymer, of one or more monomer units which 1: comprise the moiety or moieties. Particularly preferred moieties are the

N(CH

2

CO

2

A)

2 group and the -N(CHCO 2

A)

3 C1 group, wherein A is hydrogen or an alkali metal cation.

A particularly preferred embodiment of a polymer capable of chelating polyvalent cations comprises a plurality of monomer units 15 having the formula (I)

R

3 3

-(CR'R

2

CO

2

-R

4

-CR

s 5 R-CR-(CRR),-N[(CHCOA),]C1 (1)

OH

wherein

R'

2 R independently are H or a C 1 6 alkyl group, R' is a single bond or a C 1 alkylene oxy group,

R

5

R

6

R

7

R

8

R

9 independently are H or a alkyl group n is an integer from 0 to 18, A is H or an alkali metal cation, x is 2 or 3, and yis0 or 1 with the proviso that when x is 2 y is 0 and when x is 3, y is 1.

In preferred embodiments of the polymer of formula R' and R 2 are H. R 3 preferably is CH3, R s

R

6

R

7 R' and R' preferably are H. R 4 preferably is a single bond or an ethylene oxy group. A preferably is H or Na. Preferably, n is 12.

Preferred polymers include about 500 to 10,000 monomer units of formula In another preferred embodiment, the inventive polymer includes at least one comonomer unit, for example, hydrophilic comonomers such as alkyl or hydroxyalkyl (alk)acrylates. Polymers for use according to the 10 invention in producing contact lenses can include as comonomers such "hydrogel" monomers as hydroxyethyl methacrylate, hydroxyethyl methyl methacrylate, vinylpyrrolidone, glyceromethacrylate, methacrylate esters and the like. Other comonomers, such as propylene, vinyl chloride, vinylidene chloride, vinyl acetate, etc., can be employed to produce 15 polyvalent cation chelating polymers for use in producing other types of products, such as contact lens cases. Alternatively, lens cases and lens case components constructed of a hard polymer, such a polyethylene, polystyrene, polycarbonate, polyvinyl chloride or other conventional polymers, can be coated with a hydrogel polymer as described herein, a 20 polymer including about 1 to 100 wt% of a monomeric unit or units that include a polyvalent cation chelating moiety.

Specific preferred comonomeric units have a formula

(II)

R

3

-(CRR

2

CO

2

-R'

wherein R' R, R independently are H or a C, 6 alkyl group, R' is H or a C hydroxyalkyl group.

A contact lens including a polymer according to the instant invention can comprise a laminated structure in which a layer comprised of the inventive polymer is sandwiched between conventional hydrogel layers. Alternatively, a two-layer structure can include an outer layer comprised of the inventive polymer and an inner layer the layer in contact with the eye) of a conventional hydrogel-type polymer. Such a structure can increase the useful lifespan of the contact lens by inhibiting microbial penetration into and proliferation within the lens matrix, thus inhibiting damage to the lens.

ooo.

10 The present invention further provides compounds which can be :polymerized to produce a polyvalent cation chelating polymer.

Compounds of the formula (III)

I

3

CR'R

2

-C

CO2-R(-CWR -CRT-(CReR')-N[(CH2CO2A).]CI 01M) OH 20 wherein R, R 3 independently are H or a Ci., group, R' is a single bond or a C1.

6 alkylene oxy group, 5 R 6

R

7

R

8 RW independently are H or a C 1 6 alkyl group n is an integer from 0 to 18, A is H or an alkali metal cation, x is 2 or 3, and y is 0 or 1 with the proviso that when x is 2, y is 0, and when x is 3, y is 1, can be polymerized, either alone or with one or more comonomers, to produce polymers as described herein.

In particular preferred embodiments R' and R 2 are H. R 3 can preferably be CH 3

R

5 R, R 7 R' and R" can preferably be H. Preferably, R is a single bond or an ethylene oxy group. A preferably is H or Na, and n 35 preferably is 12.

Polymerization of compound (Ell) preferably is. carried out using a solvent such as glycerol, other glycols, acetic acid, alcohols, water and combinations thereof.

The instant invention also provides methods for producing compositions of matter which are capable of chelating polyvalent. cations.

The inventive methods generally include the step of reacting a compound of the formula (IV)

CR-

5

R

6

-CR

7

-(CR

8

R

9

)-N[(CH

2

CO

2 A)]C1y

UV)

wherein IRs, R', R/1 R', 8 independently are* H or a alkyl -group,.

n is an integer from 0 to 18, A is H or an alkali metal. cation, :is 2or 3,and y is 0or 1, with the proviso thatwhenxis 2, yis andwhnx is 3yis 1 with a composition of matter capable of reacting with. an epoxide.

According to a first preferred embodiment of -a method of the invention, the composition of matter capable of reacting with an epoxide is a plasma treated solid polymer having surface free radicals. In this embodiment, an article comprised of a solid polymer, such a polycarbonate, polypropylene, polyvinyl acetate or polyvinyl chloride, is exposed to a plasma at low pressure (about 0.01 to 1 mm. Hg) or in an inert gas atmosphere (N 2 Ne, Xe, etc.), which results in the formation of free radicals on the treated surface as is well known to those skilled in the art.

Next, the treated surface is exposed to a solution or a low pressure (about 0.01 1 mm Hg) vapor comprising a compound of formula This results in the formation of a derivatized solid polymer having polyvalent cation chelating groups bonded to the polymer 14 surface. Next the derivatized solid polymer is exposed to liquid water or water vapor at low pressure (about 0.1 10mm HG) in order to neutralize any residual surface free radicals on the derivatized solid polymer and stabilize the derivatized solid polymer.

In another embodiment of the inventive method, a hydrophilic ("soft") contact lens comprised of a conventional hydrogel polymer is manufactured according to any conventional method. Lenses comprised of or containing hydroxyethyl methacrylate or methacrylic acid are particularly suitable. After manufacture, but prior to extraction or S 10 hydration of the lens, the lens is contracted with a compound of formula (IV) in a liquid carrier or in neat form, preferably in the presence of a catalyst such as pyridine or triethylamine. After the esterification reaction is complete, the contact lens is soaked, preferably in an aqueous solution, to remove unreacted starting materials and side products. The lens is then dried. The matrix of the derivatized contact lens now includes polyvalent cation chelating moieties.

According to another embodiment of the foregoing method, a compound having the formula

(V)

R

3

CRR

2 C CO -R(V) wherein

R

2

R

3 independently are H or a C 16 alkyl group, and

R

4 is H or a C, hydroxyalkyl group, is reacted with a compound of formula preferably in the presence of an organic base such as pyridine or triethylamine, to afford compound

(III),

described above, which is capable of chelating a polyvalent cation and which can be polymerized to produce a polyvalent cation chelating polymer.

Compositions of matter according to this aspect of the invention can be used in many applications. For example, the polymers can be used in the manufacture of hydrogel contact lenses. The polymer can also be used to produce or form a surface coating on components of lens cases or containers used for storing ophthalmic and contact lens care solutions or contact lenses. In the alternative, the foregoing articles of manufacture can be produced using conventional polymers. Subsequently at least a portion of the surface area of such articles can then be modified as described herein, such as by plasma treatment followed by reaction with compounds of formula or by application of a coating including a polymer as described herein.

According to a preferred embodiment, the growth of ocular 10 pathogens, in particular protozoan growth, on the surface of the eye care products such as contact lenses can also be inhibited by using the present invention. For example, the contact lens can be placed in contact with a solution contained in the contact lens cases and containers made of the polymers incorporating the polyvalent cation chelating agent.

15 The invention is further illustrated by the following non-limiting examples: Example 1: Polymer having incorporated therein a polyvalent cation chelating agent 20 130 g (1 mol) of hydroxyethyl methacrylate is reacted with 343 g (1 mol) of 1, 2 -epoxy-myristylamine diacetic acid (formula IV, R" H, A H, n 12, x 2, y 0) in the presence of 130 mg of pyridine. The reaction is carried out for 50 minutes at 80"C to afford compound

CH

3 CIf C (1) (1)

SCO

2 CH CH 2 O CH 2 CH (CH 2 N (CHCO 2

H),

1

OH

100 g of compound are then dissolved in 50 g of ethylene glycol 16 solvent together with 500 mg of benzoyl peroxide as a polymerization intitiator.

The reaction mixture is exposed to ultraviolet light, and the polymerization reaction is carried out for 100 minutes at a temperature of 40"C to afford a polymer having about 100 wt of monomeric units which include a polyvalent cation chelating moiety

(-N(CH

2

CO

2 Exampl2: Polymer having incorporated therein a polyvalent cation chelating agent 100 g of compound and 100 g of hydroxyethyl methacrylate are dissolved in 100 g of ethylene glycol solvent together with 500 mg of benzoyl •peroxide as a polymerization initiator. The reaction mixture is exposed to ultraviolet light, and the polymerization reaction is carried out for 100 minutes at a temperature of 40"C to afford a polymer having about 50 wt of monomeric units which include a polyvalent cation chelating moiety.

Claims (13)

1. A method of producing a compound capable of chelating a polyvalent cation which comprises the step of reacting a compound of the formula (IV) CRsR 6 -CR 7 (CRR'),-N[(CH 2 CO 2 A)JCl (IV) O wherein R s R 6 R 7 R 8 R 9 independently are H or a Cls alklyl group, n is an integer from 0 to 18, A is H or an alkali metal cation, x is 2 or 3, and y is 0 or 1, with the proviso that when x is 2, y is 0 and 1 when x is 3, y is 1, with a compound capable of reacting with an epoxide, and selected from the group consisting of a compound of formula (V) R 3 (V) CR'R2 C CO-R' wherein R 2 R 3 independently are H or a C1- 6 alkyl group, and R 4 is H or a C-6 hydroxyalkyl group; and a plasma treated solid polymer having surface free radicals

2. A method of claim 1 wherein said compound capable of reacting with an epoxide is a plasma treated solid polymer having surface free radicals.

3. A method of claim 2 wherein said reaction comprises the steps of exposing said solid polymer to a solution or a low pressure vapor comprising said compound (IV) to form a derivatized solid polymer and (ii) neutralizing residual surface free radicals on said derivatized solid r3S^RjI polymer by exposing said solid polymer to liquid water or water vapor at low pressure. 17A

4. A method of claim 1 wherein said compound capable of reacting with an epoxide is a compound of the formula (V) (V) CR'R 2 C C0 2 -R 4 18 wherein R 2 R 3 independently are H or a C1-6 alkyl group, and R 4 is H or a C, 1 hydroxyalkyl group. A method of claim 4, wherein said reaction comprises the step of reacting said compound of the formula (IV) with said compound of the formula to form a compound of the formula (III) R3 I CR'R 2 =C SCO 2 -R 4 -CRsR-CR.-(CRR'),-N[(CH 2 CO 2 A)]C1, (n) OH* wherein RI'R 2 R 3 independently are II or a C 1 alkyl group, R 4 is a single bond-or a Ci- 6 alkylene oxy group, R R 6 R 7 'R 8 R 9 independently are H or a Ci-6 alkyl group, n is an integer from 0 to 18, A is H or an alkali metal cation x is 2 or 3, and yis 0 or 1, with the proviso that when x is 2, y is 0 and when x is 3, y is 1.

6. A compound produced by a method of claim 1.

7. A compound produced by a method of claim 2.

8. A compound produced by the method of claim 3 or claim 4.

9. An eye care product comprising a compound of claim 6. An eye care product comprising a compound of claim 7. 19

11. An eye care product of claim 10 which is a contact lens case or a container of an ophthalmic or contact lens care solution.

12. An eye care product comprising a compound of claim 8.

13. An eye care product of claim 12 which is a contact lens.

14. A method for inhibiting the growth of an ocular pathogen in an ophthalmic or contact lens eye care solution which comprises the step of contacting said solution with an eye care product of claim 9.

15. A method for inhibiting the growth of an ocular pathogen on a surface of a S contact lens which comprises the step of immersing said lens in an eye care solution contained in a contact lens case of claim DATED this 2 4 th day of May 1999 ALLERGAN SALES, INC. By its Patent Attorneys DAVIES COLLISON CAVE