AU605135B2 - Amphoteric surfactant solution for cleaning or preserving soft contact lenses - Google Patents

Description

~C5Ijoarm10 COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952-69 COMPLETE SPECIFICATION

(ORIGINAL)

Class Int. Class Application Number: Lodged: /O Complete Specification Lodged: Accepted: Published: Priority ThsdCument con tains the crZ"T dm:sf~ieunder SeCtdoi 49 and is correct for, printing.

ftejgted Art Name of Applicant: Acddress of Applicant; SA' tizal Inventor: /A.c.dress for Service,, CIBAL-GEIGY Klybeckstrasse 141, 4002 Basle, Switzerland.

FU-PAO TSAO and CHARLES A\LLEN PENLEY.

'60 IQUJEFN-- -TREET-,MELBOUR-NE 1 AUSTRALIA, 3000.

~3 7 Complete Specification for the invention entitled: AMPHOTERIC SURFACTANT SOLUTION FOR CLEANING OR PRESERVING SOFT CONTACT LENSES.

The following statement Is a fvU description of this Invention, Including 1he best meithod of performing it known to ',-Us l a 4-15760/+/CGC 1180 Amphoteric surfactant solution for cleaning or preserving soft contact lenses The present invention relates to a solution for cleaning or preserving a soft hydrophilic contact lens comprising an amphoteric 5 surfactant which also serves as a solution preservative.

a 0. A number of contact lens cleaner solutions are known in the art.

Typically such solutions employ either sorbic acid, thimerosal, t chlorhexidine, a polyquaternary germicide, a synthetic antibiotic or a conventional quaternary germicide, such as benzalkonium chloride S 10 as a preservative agent. However, these conventional preservatives have drawbacks that tend to restrict their use. For example, sorbic 0 C acid characteristically contains formaldehyde residues; thimerosal in some patients acts as an allergy sensitizer, chlorhexidine is relatively toxic; and benzalkonium chloride, over a period of time, will tend to accumulate in soft hydrophilic contact lens materials c and tend to release to the cornea to cause eye irritation.

While U.S. Patent No. 4,046,706 discloses the use of certain amphoteric imidazole surfactants in lens-cleaning solutions, such solutions characteristically also require the presence of a germicidal preservative agent of the type discussed above.

2 Surprisingly and unexpectantly, it has now been found that, while the instant amphoteric surfnctants contain a quaternary nitrogen, they do not appreciably build up or accumulate in conventional hydrophilic soft contact lenses. This is in clear contrast to conventional quaternary germicides, such as benzalkonium chlorides alkyl substituted dimethylbenzyl ammonium chloride wherein alkyl is a mixture of Cs to Cie alkyl moieties), cetylpyridinium chloride and dodecyl triethanolamine hydrochloride, which tend to accumulate in hydrophilic soft contact lens materials. Moreover, the instant amphoteric surfactants do not tend to accumulate in the eye and are characteristically less irritating than such conventional quaternary germicides.

o. It is therefore an object of the present invention of overcoming the Sooooo various drawbacks associated with the use of prior art soft contact .00000 15 lens-cleaning solutions.

0000 o0 0 0oo It is a further object of the present invention to provide a method 0 00 oo00 for cleaning and preserving soft hydrophilic contact lenses using ia effective surfactant and solution preservative amount of the instant oo amphoteric surfactants.

0 0 0 o 20 It is yet a further object of the present invention to provide 0o 4 compositions useful in such methods and their preparation.

o 0 The instant invention relates to an aqueous self-preserving soft contact lens cleaning or preserving solution comprising, as its only preservative agent, an effective surfactant and solution preserving amount of a water-soluble amphoteric surfactant of the formula I,

R-A-R

I

-C (I) 3 wherein R is alkyl, alkenyl or alkanedienyl of 6 to 18 car')on atoms each of which are unsubstituted or substituted by halo, hydroxy or amino; A is or where R' is hydrogen or lower alkyl; R' is alkylene of 2 to 6 carbon atoms which is unsubstituted or substituted by hydroxy; R 2 and R 3 are independently hydrogen or lower alkyl, which is unsubstituted or substituted by carboxy or by one or two hydroxyls, one of which may be esterified with phosphoric or sulfuric acid; and R4 is alkylene of up to 3 carbon atoms which is unsubstituted or substituted by hydroxy; or an ophthalmologically acceptable salt thereof.

In case A is or thq carbonyl group thereof is preferably attached to R.

0 0 o Alkyl of 6 to 18 carbon atoms has preferably 8 to 18 carbon atoms and is e.g. octyl, decyl, undecyl, dodecyl, tridecyl, pentadecyl, o°000. 15 hexadecyl, heptadecyl, octadecyl, or a. mixture thereof.

o oo Alkenyl of 6 to 18 carbon atoms has preferably 8 to 18 carbon atoms o""a and is e.g. octenyl, decenyl, undecenyl or heptadecenyl, such as heptadec-8-enyl.

O 0o Accordingly, in case A is the partial structure R-A- of S" 20 the compounds of formula I is represented e.g. by Cii-C17-alkyl- Oo. carbonylamino or C1y-alkenylcarbonylamino, such as lauroylamino, myristoylamino, palmitoylamino, stearoylamino, oleoylamino, or a mixture thereof, such as cocoylamino. The latter is even called cocoamido and is an extract from natural sources with an average number of 12 carbon atoms.

Halo is e.g. fluoro, iodo, or preferably chloro and bromo.

Lower alkyl has e.g. up to 7 carbon atoms, preferably up to 4 carbon atoms, and is e.g. methyl, ethyl, propyl, butyl ov tert.-butyl.

J

4- Alkylene of 2 to 6 carbon atoms is e.g. 1,2-ethylene, 1,3-propylene or 1,4-butylene. These alkylene groups may be substituted by hydroxy, such that e.g. hydroxypropylene or hydroxybutylene resul';;, preferably 2-hydroxy-1,3-propylene.

Preferably A is -C(O)NH- and R I is alkylene of 2 to 3 carbon atoms.

R

2 and R 3 are preferably independently lower alkyl which is unsubstituted or mono- or disubstituted with hydroxy, one hydroxy of which may be esterified with phosphoric acid to form the corresponding mono-, di- or tri-organophospate ester.

R4 is preferably unsubstituted alkylene of up to 3 carbon atoms and, o00 most preferably, is methylene, 1,2-ethylene, 1,1-ethylene, ooc"* 1,3-propylene or 1,2-propylene. As an alternate preferred embodiment, R' is 2-hydroxy-1,3-propylene.

So Preferred are solutions comprising, as their only preservative o o 15 agent, a surfactant of formula I wherein R is alkyl or alkenyl of 11 to 17 carbon atoms, A is or the carbonyl group of "o which is attached to R, RI is alkylene of 2 or 3 carbon atoms which oo So is unsubstituted or substituted by hydroxy, R 2 and R 3 are indepeno dently lower alkyl which is unsubstituted or monosubstituted by oo 0 20 carboxy or mono- or disubstituted by hydroxy, one hydroxy of which may be esterified with phosphoric acid to form the corresponding triorganophosphate, and R 4 is alkylene of up to 3 carbon atoms, or ,cc, an ophthalmologically acceptable salt thereof.

Especially preferred are solutions comprising, as their only preservative agent, a surfactant of formula I wherein R is alkyl of 11 to 17 carbon atoms or alkenyl of 17 carbon atoms, A is -C(0)NH-, the carbonyl group of which is attached to R, R I is alkylene of 2 or 3 carbon atoms, R 2 and R 3 are independently lower alkyl which is unsubstituted or monosubstituted by hydroxy which may be esterified with phosphoric acid to form the corresponding triorganophosphate, and RI is alkylene of up to 3 carbon atoms, or an ophthalmologically acceptable salt thereof.

Another group of preferzred solutions comprises, as their only preservative agent, a ourfactant of formula 1, wherein R is alkyl or alkenyl of 8 to 12 carbon atoms, A is the carbonyl group of which is attached to R, RI is alkylene of 2 or 3 carbon atoms, R 2 and R 3 are independently lower alkyl, and R4 is alkylene of up to 3 carbon atoms, or an ophthalmo logically acceptable salt thereof.

Preferred compounds of formula I include: N-lau roy laminop ropyl1-N, N-d ime thyl glycine; N-cocoylaminopropyl--N,N-dimethyl glycine; N- lau royl aminop ropyl1-N-c arb oxyme thyl1-N-hydroxye thyl glycine; N-ole oyl1aminopr opyl1-N- ca rboxyme thy-N-hyd roxye thyl glycine; N-3-dodecyloxy-2-hydroxypropyl-N,N-dimethyl glycine; N-cocoylaminopropyl-43-hydro,,cye thyl-3-aminopropionic acid; end tri-[ 3 co coyl aminoe thyl1-N-hydroxye thyl-N- ca rboxyme thyl) amino- 2hydroxy-propanol Iphosphate.

00 Specifically preferred are N- lau roylaminopropyl-N, N-dime thylI glycine; N-cocoylaminopropyl-N,N-dimet 3 !lI glycine and tri-[3-(No coyl amino ethy 1-N-hydro xyethyl- N-carboxyme thyl)amino- 2 -hydroxypropanol Iphosphate.

Suitably ophthalmologically acceptable salts are salts formed by the compounds of formula I e.g. with sodium chloride, potassium chloride, sodium phosphate, sodium borate, sodium bicarbonate, carbonic acid, boric acid, diethanolamine and analogous inorganic and organic acids, bases and salts conventionally employed in lens-care solutions. As the artisan can appreciate, where salts such as sodium chloride are employed, the zwitterionic inner salt form may be in equilibrium with the corresponding double salt form.

1 -6- If the solution of the ihentio. hereinbefore or hereinafter is defined as comprising a compound of formula I or a salt thereof, this definition is understood to include solutions comprising two or more compounds of formula I, two or more salts thereof or a mixture of one or more compounds of formula I and one or more of the salts thereof.

A first embodiment, according to this invention are aqueous selfpreserving soft contact lens-cleaning solutions. These may contain, in addition to the compound of formula I, other conventional additives and adjuvants. For example, suitable self-preserving cleaning solutions contain based on the total solution weight: between about 0.005 and about 2.0 by weight of a compound of formula I; between 0 and about 5 by weight of a substantially nonionic 15 surfactant; 0 between 0 and about 5 by weight of a thickener; between 0 and about 1 by weight of a chelating agent; between 0 and about 2 by weight of a buffer; O between 0 and about 2 by weight of a water-soluble salt 20 compatible with ocular tissue, and S(g) the reainer water.

Preferably, the compositions of the instant invention contain between about 0.01 and about 0.5 most preferably between about 0.02 and abo.'t 0.2 by weight compound of formula I.

When present, each of the optional components through are advantageously present in a minimum amount of about 0.01 by weight I based on total solution weight.

Suitable substantially nonionic surfactants for use as component (b) advantageously include those nonionic surfactants which are known to be generally compatible with ocular tissue, and include physiologi- .1I 7 cally acceptable poly(oxyethylene)-poly(oxypropylene) block copolymers, such as those sold under the trademark PLURONIC® by Wyandotte Chemical Corporation. Such copolymers are represented empirically by the formula: Ho(CH2CH20)a(CH(CH 3

)CH

2 0)b(CH 2 CH20) H a bc where a and c are statistically equal, the average molecular weight ranges between about 2,000 and about 16,000, and the polyoxyethylene units constitute between about 10 and 80 by weight of the molecule.

Also suitable are polyethoxylated alkylphenols, for example, wherein the alkyl moiety thereof contains between about 6 and 12 carbon o0 0oo atoms, and there are between about 3 and about 50 polyoxyethylene Sunits per molecule, as well as the corresponding alkylated methylene o bis-phenols which are polyethoxylated, such as that sold under the 15 name TYLOXAPOL® by Ruger Chemical Co.

Also suitable are polyethoxylated fatty alcohols, acidis, amintis, e.g. wherein the alkyl moiety thereof contains between 6 and o 18 carbon atoms and the molecule contains an average of between 0 about 3 and about 50 polyoxyethylene units. Preferably, the instant compositions contain between 0 and about 0.5 by weight of compo- 0, 0 nent Suitable thickeners include those conventionally employed in ophthalmic formulations and include, for example, hydroxyethylcellulose, hydroxypropylcellulose, polyvinylalcohol, polyvinylpyrrolidone, polyathyleneglycol and the like. Preferably, a thickeinr is present in an amount between 0 and about 2 by weight, more preferably between 0 and about 1.5 by weight.

-PII. i 8- Suitable chelating agents include conventional chelating agents such as ethylenediamine tetraacetic acid (EDTA) and the alkali metal, e.g. di- and tri-sodium salts (edetates) thereof, and trihydroxymethyl aminomethane, Preferably, the chelating agent is present in an amount between U and about 0.7 by weight.

Suitable buffers include alkali metal phosphates, citrates, borates, tartrates, acetates, carbonates, bicarbonates and the corresponding phosphoric acid, citric acid, boric acid, tartaric acid, and mixtures thereof. Preferably, buffers are present in an i0 amount between 0 and about 1 by weight.

Suitable water soluble salts compatible with ocular tissue (f) 6 o include especially those salts conventionally employed in providing "'ot solutions having a salt content equivalent to up to about 0.9 no sodium chloride. Preferred salts are alkali metal halides, sulfates, 15 nitrates, and phosphate salts, especially sodium chloride, potassium chloride, and mixtures thereof.

A second embodiment according to the instant invention relates to aqueous self-preserving soft contact lens preserving solutions.

SThese ccntain a solution preserving amount of the compound of formula I and a sufficient amovint of a water-soluble salt, compatible with ocular tissue, to provide a solution salt content equivalent in tonicity to about 0.5 to about 2 by weight sodium chloride.

In this alternate embodiment, it is preferred to have a sufficient amount of salt content to provide a solution salt content equivalent in tonicity to between about 0.7 and about 1,8 and most preferably between about 0.7 and about 1.0 by weight sodium chloride.

-1 9- Suitable salts which may be employed in adjusting the tonicity include alkali metal halides, sulfates, nitrates, phosphates and the like, especially the sodium and potassium salts thereof and most preferably sodium chloride, potassium chloride and mixtures thereof.

The lens preserving and storing solutions, in accordance with this embodiment, can generally contain the same additives and adjuvants in the same ranges set forth above in respect to the self-preserving contact lens-cleaning solutions, except that the lens-preserving and storing solutions advantageously contain a sufficient amount of component salt to pr-oide a solution salt content equivalent in tonicity to between about 0.7 and about 1.8 by weight sodium chloride.

The instant solutions are useful for cleaning proteinaceous, lipid and other non-proteinaceous deposits which normally accumulate on conventional hydrophilic soft contact lenses. These deposits, derived from mucus, oils, cosmetics, protein from tear fluid, and the like, unless removed, will tend to accumulate on the lenses, reducing the life of such lenses and their optical clarity, The instant compositions are highly useful in removing and solubilizing such deposits while, at the same time, are physiologically tolerable and self-preserving.

Further, the preferred instant lens-storing and preserving solutions are additionally advantageous in that the tonicity of such compositions, coupled with the nonirritating nature of the compounds of formula I to the eye, and their reduced tendency to accumulate in soft hydrophilic contact lens materials, make such compositions highly advantageous as preservative lens media, from which the lens can be placed directly into the eye without rinsing with a conventional saline solution.

The compositions of the instant invention are prepared from materials known per se. Thus, the compounds of formula I belong to a known class of amphoteric surfactants. The compositions may be prepared by conventionally mixing the ingredients.

It is a further object of the invention to provide a method for cleaning a soft contact lens comprising intimately contacting said soft contact lens with an aqueous solution containing an effective surfactant and solution preserving amount of a water-soluble amphoteric surfactant of the formula I. A convenient method of cleaning the contact lenses according to the instant invention, is to place the lens in the palw of the hand, place a few drops of solution on each lens surface, and rub the lens surfaces with the forefinger or between the thumb and forefinger, and rinse with additional solution.

It is another object of the invention to provide a method of preserving a soft contact lens by storing said lens in an aqueous solution containing a solution preserving amount of the compound of formula I and a sufficient amount of a water-soluble salt, compatible with ocular tissue, to provide a solution salt content equivalent in tonicity to about 0.5 to about 2 by weight sodium chloride.

The following examples are for illustrative purposes and are not intended to limit the scope of the invention. In each instance all percentages and parts are by weight unless otherwise specified.

Example 1: 0.5 ml of an aqueous solution containing 30 percent by weight N-cocoylaminopropyl-NN-dimethyl glycine (Monaterice CAB by Mona Industries, Inc.) is combined with 2,613 g sodium chloride, 1.25 g sodium tetraborate, 1.75 g boric acid, 1.0 ml tyloxapol, g hydroxyethyl cellulose and 2.5 g disodium edetate. Water is 11 added -to a total solution volume of 500 ml with stirring, The re.,ulting solution is filter sterilized using ultrafiltration to obtain a solution having a pH of 7.2 and an osmolarity of 304.

Excam le 2: 0.5 m! of an aqueous solution containing 30 percent by weight N-iauroylamrinopropyl-N,N-dimethyl glycine (MonatericO LMAB) is combined with 2.685 g sodium chloride, 1.25 g tyloxapol, 3.5 g hydroxyethyl cellulose, and 2.5 g of dis-idium edetate. Water is added to a total solution volume of 500 ml with stirring. The resulting solution is filter sterilized using ultrafiltration to obtain a solution having a pH of 7,2 and an osmolarity of 298, Example 3: 0.5 ml of an aqueous solution containing 30 percent by weight N-cocoylaminopropyl-N,N-dimrethyl glycine is combined with 3.45 g sodium chloride, 0.7 g sodium tetraborate, 2.7 g boric acid and 1.0 g disodium edetate, Water is added to a total solution volume of 500 ml wiL.h stirring. The resulting solution is filter steriliz~d using ultrafiltration to obtain a solution having a pH of 7.2 and an Psmolarity of 306.

Example,41 0.5 ml of an aqueous solution containing, 30 percont by weight N-lauzroylaminopropyl-N,N-dimethyl glycine is combined with 3.18 g sodiu,'n chloride, 0,7 g sodium tetraborate, 2.7 g boric acid and 1.0 g disodium adetate. Water is added to a total solution Volvne of 500 ml with stir~ringi The resulting solution is filter sterilized using ultrafilttation to obtain a solution havitig a pUl of 7,21 and an osmolarity of 310.

Exml ;0.3 g of~ an aqueous solution containing 30 w4eight percent of tri-f 3-.(N-cocoylaniinoethyl-N-hydro: yethyl-N-carboxymothyl) amino-, 2hydroxypropanol) phosphate~ (Nonaqoat P-TL by Monma Tndsiis Inc.,) is combined with 0.24 g tnis-(hydrox-ymhtlil)aminomietht, g bor~ic acid and YJ3 g sodiHOt. Chloride and diluted wit 1 sufficaient water to obtain. a total golutioti volume oft 100 01.

12 Example 6: 1,5 g of an aqueous solution containing 30 percent by weight N-lauroylaminopropyl-N,N-dimethyl glycine, 2.685 g sodium chloride, 1.25 g sodium tetraborate, 1.75 g boric acid, 1.0 g tyloxapol, 3.5 g hydroxyethylcellulose, and 2.5 g disodium edetate are combined. Sufficient water is addedd with stirring to obtain a total solution volume of 500 ml. The pH of the solution is 7.43, which is adjusted with 0.5 N HC1 to a pH of 7.23.

Example 7: The procedure of example 6 is repeated and identical amounts of ingredients are used except that 2.5 g of an aqueous solution containing 30 percent by weight N-lauroylaminopropyl-N,Ndimethyl glycine is employed. Upon dilution to 500 ml with water, the pH is 7,4 which is ad' sted with 0.5 N HCl to a pH of 7.20.

E ample8: 1.5 g of an aqueous solution containing 30 percent by weight N-lauroylaminopropyl-N,N-dimethyl glycine, 1 g disodium edetate, 2.7 g boric acid, 0,70 g sodium borate and 3.15 g sodium chlorid? are combined and diluted with sufficient water, with stirring, to make a total solution volume of 500 ml. The solution has a pH of 7.22 and an osmolarity of 319.

:Exmaple 9: The compositions of examples 6, 7 and 8 are evaluated in accordance with the modified Draie rabbit eye test (Food, Drug, and Cosmetic Law Reports 233) in order to access potential irritation.

The three solutions are each determined to be "non-irvcitating" in this test.

L

Claims (9)

1. An aqueous self-preserving soft contact lens cleaning or preserv- ing solution comprising, as its only preservative agent, an effec- tive surfactant and solution preserving amount between about 0.005 and about 2.0 by weight of a water-soluble amphoteric surfactant of the formula I, R-A-R R4 -COOe (I) wherein R is alkyl, alkenyl or alkanedienyl of 6 to 18 carbon atoms each of which are unsubstituted or substituted by halo, hydroxy or amino; A is or where R' is hydrogen or lower alkyl; R 1 is alkylene of 2 to 6 carbon atoms which is unsub- stituted or substituted by hydroxy; R 2 and R 3 are independently hydrogen or lower alkyl, which is unsubstituted or substituted by carboxy or by one or two hydroxyls, one of which may be esterified with phosphoric or sulfuric acid; and R 4 is alkylene of up to 3 carbon atoms which is unsubstituted or substituted by hydroxy; or an ophthalmologically acceptable salt thereof; and an ophthaliologically acceptable water sL-uble salt which is compatible with ocular tissue in an amount to provide a solution salt content equivalent in tonicity to about 0.5 to 2.0 by weight sodium chloride.

2. A solution according to claim 1 wherein R is alkyl or alkenyl of 11 to 17 carbon atoms, A is or the carbonyl group of i which is attached to R, R 1 is alkylene of 2 or 3 carbon atoms which is unsubstituted or substituted by hydroxy, R 2 and R 3 are indepen- dently lower alkyl which is unsubstituted or monosubstituted by carboxy or mono- or disubstituted by hydroxy, one hydroxy of which may be esterified with phosphoric acid ti form the corresponding triorganophosphate, and R 4 is alkylene of up to 3 carbon atoms. 14

3. A solution according to claim 1 wherein R is alkyl of 11 to 17 carbon atoms or alkenyl of 17 carbon atoms, A is -C(O)NH-, the carbonyl group of which is attached to R, R 1 is alkylene of 2 or 3 carbon atoms, R 2 and R 3 are independently lower alkyl which is unsubstituted or monosubstituted by hydroxy which may be esteri- fied with phosphoric acid to form the corresponding triorganophos- phate, and R 4 is alkylene of up to 3 carbon atoms.

4. A solution according to claim 1 wherein R is alkyl or alkonyl of 8 to 12 carbon atoms, A is the carbonyl group of which is attached to R, RL is alkylene of 2 or 3 carbon atoms, R 2 and R 3 are independently lower alkyl, and R4 is alkylene of up to 3 carbon atoms.

A solution according to claim 1 wherein the compound of formula I is selected from N-lauroylaminopropyl-N,N-dimethyl glycine; N-cocoylaminopropyl-N,N-dimethyl glycine and tri-[3-(N-cocoylamino- ebhyl-N-hydroxyethyl-N-carboxymethyl)amino-2-hydroxy-propanol]phos- phate.

6. The solution of claim 1 comprising between about 0.005 and about 2.0 by formula I; between 0 and about 5 by weight of a surfactant; between 0 and about 5 by weight of a between 0 and about 1 by weight of a between 0 and abiut 2 by weight of a between 0 and about 2 by weight of a compatible with ocular tissue, and the remainder water, weight of a compound of substantially nonionic thickener; chelating agent; buffer; water-soluble salt

7. The solution of claim 1 as disclosed in any of the examples. I7 I 15

8. A method of cleaning a soft contact lens comprising intimately contacting said soft contact lens with a solution according to any one of claims 1 to 7.

9. A method of preserving a soft contact lens comprising intimately contacting said soft contact lens with a solution according to any one of claims 1 to 7. A process for manufacture of a solution according to any one of claims 1 to 7 by conventionally mixing the ingredients. DATED the 18th day of April, 1990. CIBA-GEIGY AG By Its Patent Attorneys ARTHUR S. CAVE CO. si ~~fi