CA1231069A - Microbial enzymatic contact lens cleaner and methods of use - Google Patents

Abstract

MICROBIAL EMZYMATIC CONTACT LENS CLEANER
AND METHODS OF USE

ABSTRACT OF THE DISCLOSURE
Proteinaceous tear films and debris are removed from contact lenses with aqueous solutions of bacterial proteolytic and carbolytic enzymes, principally protease and amylase with or without lipase. The solutions are substantially odor-free, non-allergenic, require no activator/stabilizer and are completely water soluble.

Description

~23~()6~3 BLP:l04 MICROBIAL ENZYMATIC CONTACT LEWIS CLIP
AND METHODS OF USE

BACKGROUND OF THE INVENTION
..
The present invention relates generally to lens cleaning compositions and methods of use, More specifically, this invention is concerned with new enzyme cleaners and methods for effective removal of film build-up and debris from contact lenses which may be present asproteinaceous-carbohydrate-lipid containing deposits.
Cleaning compositions for contact lenses generally fall into one of three categories: surfactant cleaners;
oxidative cleaners and enzyme cleaners. Surfactant cleaners are widely used, for example, by placing a drop of solution on a lens, rubbing the lens between the fingers followed by rinsing. Although such cleaners are usually safe and not harmful to lenses when used properly, most surfactan~ cleaners are not effective in the removal of protein deposits.
The second type of cleaning system involves oxidative products containing, for example, per sulfates and perorates. They may be used either by cold soaking or with boiling for about 30 minutes. This type type of cleaning system is mainly effective in removing non-protein deposits from contact lenses. They are generally non-toxic, however, oxidizing agents can have a deleterious effect on lenses. One possible explanation is that they may oxidize the basic polymer chain by the introduction of pH-sensitive molecular groups.
The third method of cleaning is with enzymes.
Enzyme cleaners are generally viewed as being efficacious, safe and capable of removing the principal component of contact lens film and debris, namely protein. Some also have the ability to remove carbohydrate and lipid deposits from contact lenses.
Heretofore, the supply of proteolytic, carbolytic and lipolytic enzymes e.g.. pro teases, amylases and lapses for use in contact lens cleaning solutions was restricted to plant and animal sources. Cleaning solutions prepared from plant and animal derived enzymes have several lo shortcomings. In most instances, they either impart an unpleasant odor to the cleaning bath or develop an odor after a few hours of use. In some cases, plant and animal pro teases and amylases will discolor lenses.
Contact lens cleaning solutions prepared with plant 15 and animal derived pro teases like pa pain, chymopapain, pancreatic, trypsin, chymotrypsin, pepsin, ficin, carboxypeptidase, aminopeptidase, and bromelin are described in several patent publications e.g. USE.
Patent 3,910,296; US Patent Publication GO 2,088,581;
Japanese application 113,233 published May 31, 1975 as Cook 64,303 and US. Patent 4,096,870. In addition to the patent citations, enzymatic lens cleaners prepared with pro teases from pork, namely pancreatic have been commercially available from Alcoa Laboratories. Enzymatic contact lens cleaners prepared with plant pro teases i.e.
pa pain have also been available from Allergen Pharmaceuticals under the registered trademark Softens Enzymatic Cleaning Tablets. Although these preparations are generally effective in cleaning contact lenses, they have shortcomings in addition to those previously mint owned That is, besides the propensity for unpleasant odors and potential for discoloring lenses, cleaners containing pro teases like pancreatic from pork or beef can induce an allergic response among some users. In addition, solutions containing pancreatic have a tendency I I

to become cloudy and turbid.
Plant pro teases for example Appian, normally require lengthy cleaning cycles ranging from 4 to 12 hours in order to remove film and debris from lenses. Such lengthy cycles can be an inconvenience to the user. In addition, cleaning solutions prepared with plant an animal pro teases require the application of heat e.g. 80C which is needed not only to disinfect the lenses, but also to inactivate the enzyme.
lo contact lens cleaners containing enzymes also require stabilizers/activators. For example, pa pain requires Sistine. Pancreatic requires calcium salts. Without the use of an activator pa pain and other similar plant enzymes will remain dormant. Activators like Sistine are hydroscopic and have a tendency to pick-up moisture creating manufacturing difficulties. Such enzyme products can only be manufactured and packaged under stringent standards to eliminate any moisture from entering the packaging otherwise it will attract and shorten the shelf life of the cleaner.
Microbial rot eases derived from Bacillus and Stratum bacteria and Aspergillus mold have been previously described. US. Patent 3,590,121 discloses an effervescent tablet used for making mouthwash. The tablets and solutions of this patent employ a neutral protozoa referred to as a metallo-enzyme having an optimum activity at a pi of G to 8. Because metals are an integral part of the enzyme, its activity is inhibited by the presence of chelating agents which are customarily employed in contact lens cleaning preparations to bind calcium an other unwanted metals from reacting with proteins and depositing on lenses. Consequently, enzymes josh are inhibited by chelating agents, like those described in US. 3,590,121 are generally unsatisfactory 123~ 69 for use with contact lenses.
US. 3,717,550 describes the preparation of liquid concentrates of bacterial protozoa and/or aimless. The liquid concentrates are used for making such products as household detergents.
Accordingly, there is a need for safer, more dependable enzyme cleaning preparations which will offer a broad spectrum of cleaning capability for efficient removal ox at least protein and carbohydrate films and lo debris from contact lenses. The enzymes should be both stable in solution, remain active at elevated temperatures and be compatible with other components of toe cleaning composition. Preferably, the enzyme system should not depend on the use of activators which may lead lo to auto digestion with the enzyme, limiting the shelf-storage life. Similarly, the cleaning process should be convenient for the user eliminating the need for protracted soaking periods by allowing the user the flexibility of shorter cleaning times. The enzyme cleaning composition should also be free or substantially free of odor and not cause discomfort to the wearer when the lenses are reinserted into the eyes. They should not cause irritation or allergic response as a result of residual amounts of enzyme on the lens surface.
MARY OF THE INVASION
In accordance with this invention, there is provided an enzymatic contact lens cleaner containing an effective, non-toxic amount of a protozoa derived from a Bacillus, Streptomyces or sprawls microorganism, such that when mu dissolved in an aqueous solution will effectively remove at least protein and carbohydrate films and debris from contact lens surfaces. The enzyme cleaners may contain protozoa alone derived from the above genera of bacteria or mold. The enzyme will preferably be comprise of a mixture predominantly of protozoa and aimless, and optionally, a minor amount of Lopez.
This invention also contemplates various tablets including effervescent and noneffervescent water soluble tablets, including granules and powders which contain in addition to the usual inert binders, excipients, lubricants etc., other desirable functional additives, like buffers, preservative, chelating agents, toxicity adjusters, and the like, such that when dissolved in water a preserved isotonic solution is formed and ready to be used for lens cleaning. Similarly, the present invention contemplates water-soluble microbial protease-amylase tablets particularly suitable as heat unit enzyme tablets for high temperature cleaning/disinfection of lenses. Such tablets may be added to aqueous isotonic lens soaking or cleaning solutions for cold soaking or high temperature cleaning and disinfecting. These soaking and cleaning solutions which the enzyme tablets are added to may contain preservatives, chelating agents, surfactants, pal buffers, toxicity adjusters, etc.
The microbial protease-containing lens cleaning solutions are especially effective in digesting and removing denatured protein and carbohydrate films and debris from contact lenses without enzyme activators, and therefore, present fewer Manufacturing and pacliaginO
problems in formulating the various cleaning preparations contemplated herein.
The enzymatic contact lens cleaners of the present invention are especially effective in removing contact lens film and debris in one hour or less by high temperature cleaning methods. In addition, the bacterial enzyme cleaners may perform with little or no residual binding or concentrating onto lens surfaces, and therefore, eye tissue sensitivity normally manifested as stinging and inflammation are virtually eliminated.

~L23~ 9 .

DESCRIPTION OF THE PREFERRED EMBODIMENTS
This invention relates to cleaning solutions for use with most contact lenses, including hard and 80ft lenses, as well as the newer hard gas permeable type contact lenses, such as described in US. patent 4,327,203. The invention also relates to those soft lenses generally referred to as extended-wear lenses containing 55 percent or more water content. The term "soft contact lens" as used herein generally refers to those contact lenses which readily flex under small amounts of force and return to their original shape when that force is released.
Typically, soft contact lenses are formulated from poly(hydroxyethyl methacrylate) which has been in the preferred formulations, cross-linked with ethylene glycol dimethacrylate. For convenience, this polymer is generally known as FUME. Soft contact lenses are also made from silicon polymers cross-linked, for example, with dim ethyl polysiloxane. Conventional "hard contact lenses", which cover only the cornea of the eye, usually consist of poly(methyl methacrylate) cross-linked with ethylene luckily dimethacrylate.
The enzyme cleaners are derived from microorganisms and include various species of Bacillus and Streptomyces bacteria and Aspergillus mold. Species of microor~anisims within the foregoing genera known to form mainly protozoa and aimless are intended and include such members as B.
subtilis, B. licheniformis, As~er~illus ours, ._ _ _ _ _____ _ ______ __ __ _____ __ ___ Assyria us nicer, Stratum rises, StrePtomyces Aryan. Protozoa and aimless derived from B- licheniformis are generally preferred. The compositions herein may contain only protozoa, but microbial enzymes in pure or nearly pure form are not always readily available. Thus, most commercially available products containing mixtures lo )69 predominantly of protozoa and then aimless, including some Lopez are satisfactory. The aimless is preferably I-aimless because aimless it more sensitive to heat.
The microbial enzyme products contemplated herein are commodities of commerce and are readily available from a number of manufacturers under various designations. For instance, Enzyme Development Corporation, Copyright, JOY
produces protozoa under the Enzeco trademark including a food grade of protozoa, "PROTOZOA A I" derived from I.
lo licheniformis which also contains aimless activity. Finagle protozoa produced from Asper~illus ours is also available under the Enzeco trademark. Finagle protozoa is also available from Corning BOO Systems, Corning, NAY.
under the Rhizome 41 trademark. Rhizome P-11 a protozoa derived from AsPergillus flavus-oryzae is also available.
Protozoa under the Rhizome family of products include those grades designated as B-6; PI; and P-53 produced from By subtilis. Useful pro teases are also commercially available from the International Enzyme Company, Nagoya, Japan under the trademarks Amino; Prism and Nulls, and from GOB. Fermentation Industries, Des Plainest Illinois under the trademarks Maxatase and Prolate.
The protozoa should be active at a pi range of from 5 to about 8.5. The optimum riven pi for a given enzyme product may be above or below this range. But, because of the most preferred safe range for cleaning contact lenses is about the neutral range the importance of proteolytic activity in the highly alkaline and acidic pi ranges is not critical.
Preferably, the protozoa should not be inhibited when in the presence of a chelating agent, such as in the case of metallo-enzymes.Protease activity according to this invention may be expressed in cozen units and is determined by the widely known procedure involving the digestion of cozen. The procedure for assay of neutral ~LZ3~)6~3 protozoa activity it described in the Journal of General Physiology, 30 (1947) 291 and Methods of Enzy~ology, 2, Academic Press, New York 33 ~1955).
The enzymes preferably remain active when exposed to elevated temperatures. That is to say, the methods disclosed herein provide for cleaning lenses at ambient temperature conditions using the "cold" soaking technique, as well as elevated temperature conditions using high temperature cleaning/disinfection methods.
The enzymatic cleaners containing mainly the protozoa and aimless characterized hereinabove are employed in amounts sufficient to digest and remove films and debris from contact lenses. That is, the cleaning preparations should contain sufficient enzyme activity that when dissolved in the lens cleaning bath will remove virtually all pretenses and carbohydrate debris and film by either cold soaking or at elevated temperatures.
The enzyme concentration in solution will usually range from about 0.0001 and 5.0% wlv. Enzyme tablet preparations e.g. non-effervescent water soluble heat unit tablets, effervescent tablets, granules or powder packets will generally contain from about 0.01 to about 500 my of enzyme, and more particularly, from about 10 to about 100 my of enzyme wherein the protozoa activity ranges from about 30 to 80 cozen units/mg of enzyme, and more preferably, about 40 to about 70 cozen units my of enzyme.
As previously indicated, the present invention contemplates various remeasured compositions as convenient means for dispensing a sufficient amount of enzyme for cleaning lenses. They include, for example, soluble tablets which dissolve in aqueous solutions without effervescing; effervescent tablets including granules and powders each of which contain sufficient ~23~(~6g composition for a jingle cleaning cycle. Also included are large effervescent tablets which may be scored for easy fracturing whereby each half tablet can be used in making a cleaning solution for each lens placed in a lens case.
In preparing powders and various tablets the enzyme powder is formulated with known tablet binders or excipients and may have inert carriers, disintegrants and salts which will effervesce in aqueous solution. Methods and materials for making such tablets and powders are all well established practices in the tablet making art and their identification and selection are matters of routine skill.
In addition to the microbial enzymes, the tablets, granules and powders may also be formulated with one or more other ingredients to assure optimum cleaning activity without adverse affects to the lens or to the users eyes.
For example, the enzyme preparations may contain a variety of additives, such as toxicity adjusters, buy ens, preservatives, surfactants, chelating agents to assure stability and sterility of the cleaning solution, complete dispersion of residual lipid deposits and the like.
Enzymatic cleaning tablets and powders containing such complete formulations are highly convenient to the user, since a cleaning solution can be prepared by simply dissolving in distilled water. For example, tablets granules and powders may be formulated with toxicity agents to approximate the osmotic pressure of normal lukewarmly fluids which is equivalent to a 0.9% solution of sodium chloride or 2.5% glycerol solution.
It may also be advantageous to include a disinfectant/germicide as a means for preserving the cleaning solution. A preservative is added in sufficient amount to provide a concentration in the cleaning bath ranging from about 0.00001 to about 0.5 weight percent, :~Z3~6~

and more preferably, from about 0.0001 to about 0.1 weight percent. Suitable preservatives include, but are not limited to thimerosal, sorbic acid, l,5-pentanedial, alkyd triethanolamines, phenylmercuric salts, e.g. nitrate, borate, acetate, chloride and mixtures thereof. Other suitable compounds and salts may be used which are soluble on water at ambient temperature to the extent of at least 0.5 weight percent. These salts include the gluconate, the isothionate (2-hydroxyethanesulfonate), format, acetate, glutamate, succinamate, monodiglycollate, dimethanesulfonate, lactate, dii~obutyrate, glucohep-donate.
Suitable buffers include, for example, sodium or potassium citrate, citric acid, boric acid, sodium borate, it sodium bicarbonate and various mixed phosphate buffers, including combinations of Nope, Nope and KH2P04.
Generally, buffers may be used in amounts ranging from about 0.05 to about 2.5%, and more preferably, from about 0.1 to 1.5% by weight.
Complete tablets and powders preferably contain in addition to the toxicity agents, buffers and preservatives previously described, various sequestering or chelating agents to bind metal ions, such a calcium which might Sirius react with protein and collect on lens surfaces.
Lthylenediaminetetraacetic acid (ETA) and its salts (disodium) are preferred examples. They are normally added in amounts sufficient to provide a solution containing from about 0.01 to about 2.0 weight percent.
Although the microbial enzyme cleaning preparations described herein can be readily prepared with many of the abuve-identified additives, such that when dissolved in distilled water for example, will provide a complete, preserved isotonic-enzymatic cleaning solution, as a further preferred embodiment these tablets, powders, etc., I

may be prepared free of such additives, including toxicity agents, buffers, etc. That is, the various water soluble tablets, granules and powders may be formulated with suitable inert ingredients, such as carriers, lubricants, binders or excipients, like polyethylene glycol, sodium chloride eta" commonly used in the tablet making art.
This embodiment is especially suitable for use in conjunction with other aqueous lens care products, like wetting solutions, soaking solutions, cleaning and conditioning solutions, as well as all purpose type lens care solutions. Such products contain, for instance, toxicity agents, pi buffers, cleaning and wetting agents, sequestering agents, viscosity builders, etc. Thus, effervescent tablets formulated, for example, with a mixture of the microbial enzymes and effervescent salts like citric or tartaric acids and sodium bicarbonate may be dissolved in any of the readily available OTC solutions e.g. .., isotonic-preserved saline solution containing a chelating agent, such as disodium ETA and a surfactant.
Microbial enzyme cleaning activity may be supplemented with a surfactant type cleaner which may be used before or after enzymatic cleaning to remove any residual lipid deposits. In those instances where there has been a heavy build-up of denatured tear film and debris on lenses the lipolytic activity of the enzyme may be supplemented by use of a surfactant-type lens cleaner When surfactants are used, neutral or non-ionic types are preferred for their cleaning and conditioning properties which are usually present in amounts up to 15 weight percent. Examples of suitable surfactants include, but are not limited to polyethylene glycol esters of fatty acids, e.g. coconut, polysorbate, polyoxyethylene, or polyoxypropylene ethers of higher alikeness (~12-C18).
Examples of preferred surfactants include polysorbate 20 (available under the trademark Tweet 20), polyoxyethylene ~L23~65 (23) laurel ether (Brim 35), polyoxyethylene (40) Stewart (My; I polyoxyethylene (25), propylene jackal Stewart (Atlas 2612).
One non-ionic surfactant in particular consisting of a poly(oxypropylene)-poly(oxyethylene) adduce of ethylene Damon having a molecular weight from about 7500 to about 27,000 wherein at least 40 weight percent of said adduce is poly(oxyethylene) has been found to be particularly useful in cleaning and conditioning both soft and hard lo contact lenses in amounts from about 0.01 to about 15 percent. Such surfactants are available from BASS-Wyandotte under the registered trademark --Tetronic.
The microbial protease-amylase and optional Lopez contact lens cleaners provide several benefits, including substantially odor-free, non-allergenic, require no additional activator or stabilizer and are completely water soluble. In addition, the microbial protozoa-aimless enzyme cleaners may be conveniently used in conjunction with contact lens heat disinfection units, such as those available from Bausch Lomb under the Austrian trademark which has, for example, a one hour cleaning cycle where lenses in solution are heated up to about 80C and then allowed to cool. Thus, high temperature cleaning and disinfection may be carried out with the enzyme cleaners of the present invention in one hour or less without the usual 2 to 12 hour presoaking and final disinfection. The shorter cleaning cycles are especially desirable for use in conjunction with extended wear lenses which can be cleaned with the microbial protease/amylase product in 30 minutes at a peak temperature e.g. ... 70C, thereby reducing the possibility of physical damage, such as discoloration to the lenses. Details of this one-step cleaning method are described in cop ending Canadian application SUN. 465,505, filed on :-3 ~3~06 .

even date herewith.
The following specific examples demonstrate the composition and methods of the instant invention. It is to be understood that these examples are for illustrative purposes only and do not purport to be wholly definitive as to conditions and scope.

EXAMPLE
In order to study the effectiveness of bacterial protozoa in removing pretenses film deposits and debris from contact lenses compressed, water-soluble heat unit tablets are first prepared with each tablet containing about 18 my of PROTOZOA A I enzyme commercially available under the Enzeco trademark from Enzyme Development Corporation, Copyright, slew Jersey. The enzyme it derived from B. licheniformis and contains principally pretty and -aimless activity. The protozoa activity is approximately 53 cozen un~ts/mg. The enzyme is stable at a pi of between 5.0 and 10Ø
The enzyme powder it first granulated with a sufficient amount of a pharmaceutical grade polyethylene glycol (4000) or other suitable binder and lubricant. The granulated fines are then formed into compressed tablets with each tablet weighing approximately 30 my.

EXPEL II
A clear artificial tear solution is prepared consisting of 0.2 grams of lysozym~/100 ml of electrolyte.
The electrolyte is a stock solution prepared from sodium bicarbonate 2.2 gel, sodium chloride 7 gel, calcium chloride 0.0005 gel and potassium chloride 1.5 gel.
Six (6) polymacon soft contact lenses commercially 3 available from Bausch & Lomb under the registered trademark Softens are microscopically inspected before coating with the lyceum solution. The lenses are then 'I' :1.23~(~69 soaked in the lysozyme solution for 30 to 60 minutes at room temperature. The lenses are then placed individually into the wells of Lensgard carrying cases and placed into Bausch & Lomb Austrian heat units in order to denature the lysozyme protein. The coated lenses are then placed in other Lensgard carrying cases and covered with sorbic acid preserved sterile isotonic saline solution containing Tetronic 1107 surfactant. A single tablet prepared in Example I is dispensed into each well of the lo carrying case and the caps for the cases tightly affixed.
Each case is subjected to a heat cycle in a Austrian Lotte unit having a one hour heating cycle with a maximum temperature of 80C followed by a cooling off cycle. At the conclusion of the heating cycle the lenses are removed from the cases rubbed and rinsed with sorbic acid preserved sterile isotonic solution containing Tetronic 1107 surfactant. Each of the lenses are then microscopically inspected. The denatured protein on all the test lenses is completely removed. No defects or apparent discolorations are observed in each of the six lenses.

EXAMPLE III
In order to evaluate the compatibility of the enzyme cleaning tablets on soft contact lenses a first experiment is conducted with the enzyme cleaner only. second study is performed to evaluate the effects of the combination of the enzyme, preserved lens cleaner and heat on soft contact lenses.
Six (6) polymacon Softens contact lenses are 3 microscopically inspected for possible defects and discoloration and are then placed in the wells of three Lensgard lens carrying cases. Each of the lenses is then covered with a sorbic acid preserved isotonic saline ~.Z3~1369 60lutlon containing Tetronic 1107 surfactant. Thirty (30~
milligrams of polyethylene glycol us then added to the well of the first case; a water soluble enzyme tablet from Example I it placed in each of the wells of the second case and nothing further it added to the third carrying case. The caps for the wells are placed on each of the cases which are then subjected to a single one hour heating cycle in an automatic Austrian heat unit.
The above procedure is repeated for five times using loathe same lenses while replenishing the preserved saline solution, polyethylene glycol and enzyme at the beginning of each of the cycles. At the conclusion of each of the cycles the lenses are microscopically inspected. rho defects or discolorations are observed on any of the six lionizes and the lenses remained unchanged for the duration of the study.

EMPLOY IV
An oscular irritation study is performed using fluoresce in dye retention on corneas of rabbit eyes fitted wow contact lenses treated in cleaning solutions prepared with the Enzeco A heat unit enzyme tablets of Example I.
The yes of three rabbits are fitted with Softens brand polymacon contact lenses, three of which are cleaned by heating in an Austrian heat unit containing the enzyme tablets from Example I dissolved in a sorbic acid preserved isotonic saline solution commercially available from Bausch & Lomb under the trademark Sensitive Eyes.
The control eye is fitted with a lens heated with a Sensitive Eyes solution only. All eyes are examined microscopical each day before insertion and after removal of the lenses which are worn on an average of six hours per day for five days. Fluoresce in staining is performed in conjunction with U/V light prior to initiation of the study, repeated after three days of :~3~L069 wear and again at the completion of the study. Any oscular irritation is detected by dye absorption using slit lamp microscopy.
All eyes exhibit minimal conjunctival redness probably due to lens wear and manipulation. No positive fluoresce in staining is observed. Jo positive reactions are observed microscopically throughout the study.

EXAMPLE V
Comparative studies are conducted to evaluate the cytotoxicity of lens cleaning solutions prepared with the heat unit tablets of Example I. The studies utilize the Ajar Overlay Assay technique published in the Journal of Pharmaceutical Sciences, Volume 54 (1965) pages 1545-1547 by W. L. Guess et at. Four polymacon Softens contact lenses are soaked in solution prepared by dissolving enzyme tablets in the wells of Lensgard lens cases having sorbic acid preserved isotonic saline solution containing Tetronic 1107 surfactant. An additional four lenses are placed in cases containing only the preserved saline-Tetronic solution which serve as controls. The lenses reheated for one cycle in Austrian heat units and rinsed in the preserved saline-Tetronic solution, then heat treated for an additional cycle and rinsed again before being plated onto L-929 mouse fibroblast cells to observe any Jo lying of the cells.

~3~()6~9 TABLE
Width of DecolQrlzed Zone Lens Solution Response Percent of Cells Lucid Enzyme Non-cytotoxic 0/0

2 Enzyme " 0/0

3 Enzyme " o/o

4 Enzyme " /
Control " 0/0 6 Control " 0/0 7 Control " /
8 Control " 0/0 The absence of a decolonized zone indicates the lack of lucid cells and absence of a cytotoxic response.

EXAMPLE VI
Effervescent Enzyme Tablets Effervescent enzyme cleaning tablets are made by first preparing an effervescent excipient containing sodium bicarbonate, citric acid and sodium chloride in a weigh ratio of 3:1:1. Each of the salts is finely ground separately in a mortar and then mixed together with the aid of a mortar and pestle. A small amount of distilled water e.g. .~. <0.5 ml is added to the mixture and further lo blended to initiate molecular interaction of the salts.
The mixture is spread evenly on a glass plate and placed in a vacuum oven for 2 to 3 hours at 60C. The mixture is then finely ground in a mortar and blended with Enzeco Protozoa A I enzyme powder in a ratio of excipient to lo enzyme of 2:1 to provide 100 my of enzyme per tablet.
Tablets are then made by compressing at 2500 prig.
The above tablets are then tested for dissolution time; solution appearance and effervescence characteristics. Dissolution in 10 ml of distilled water requires 37 seconds; a white foam appears initially but settles shortly thereafter to provide a clear and colorless solution. Dissolution of the tablet occurred uniformly.
While the invention has been described in conjunction with specific examples thereof, this is illustrative only.
~ccordin2ly, many alternatives, modifications and variations will be apparent to those skilled in the art in light of the foregoing description, and it is therefore intended to embrace all such alternatives, modifications to no variations as to fall within the spirit and broad scope of the appended claims.

Claims (25)

WHAT IS CLAIMED IS:

1. A method of cleaning a contact lens, which comprises contacting the lens with an effective amount of an activator free protease-containing solution, said protease being derived from a Bacillus, Streptomyces or Aspergillus microorganism.

2. The method of claim 1 wherein the protease solution includes other enzymes derived from said microorganisms.

3. The method of claim 2 wherein the enzyme-containing solution is comprised predominantly of protease and amylase.

4. The method of claim 2 wherein the microbial enzyme-containing solution includes lipase.

5. The method of claim 3 wherein the enzyme-containing solution includes one or more ingredients selected from the group consisting of a tonicity agent, a buffer, a preservative, a surfactant and a chelating agent.

6. The method of claim 3 wherein the enzymes are derived from Bacillus licheniformis.

7. The method of claim 3 wherein the enzymes are derived from Aspergillus oryzae.

8. The method of claim 3 wherein the enzymes are derived from Streptomycies griseus.

9. The method of claim 2 wherein the enzyme-containing solution is prepared by dissolving a tablet, powder or granule in an aqueous solution to provide an enzyme concentration of about 0.0001 to about 5.0% w/v.

10. The method of claim 9 wherein the enzyme solution is prepared from an effervescent tablet or granules.

11. The method of claim 9 wherein the enzyme solution is prepared from a water soluble, non-effervescent tablet.

12. The method of claim 9 wherein the enzyme tablet, powder or granules comprise protease and amylase derived from Bacillus licheniformis.

13. The method of claim 12 wherein the enzyme tablet, powder or granules includes one or more additional ingredients selected from the group consisting of a binder, a carrier, an excipient, a lubricant, a disintegrant, a tonicity agent, a buffer, a preservative, a surfactant, a chelating agent and an effervescent salt.

14. A contact lens cleaning tablet comprising from about 0.01 mg to about 500 mg of a protease free of activator derived from a Bacillus, Streptomyces or Aspergillus micro-organism, said protease remaining active when in the presence of a chelating agent.

15. The cleaning tablet of claim 14 comprising protease and other enzymes derived from said microorganisms.

16. The cleaning tablet of claim 15 wherein the microbial enzymes are predominantly protease and amylase.

17. The cleaning tablet of claim 16 which is an effervescent tablet or water soluble, non-effervescent tablet.

18. The cleaning tablet of claim 16 wherein the enzymes are derived from Bacillus licheniformis.

19. The tablet of claim 17 including one or more ingredients selected from the group consisting of a binder, a carrier, an excipient, a lubricant, a disintegrant, a tonicity agent, a buffer, a preservative, a chelating agent and an effervescent salt.

20. The tablet of claim 19 including an excipient or tablet binder which tablet provides a substantially isotonic solution when dissolved in an aqueous solution.

21. A non-effervescent contact lens cleaning tablet comprising an effective concentration of an activator free pro-tease and amylase derived from a Bacillus bacteria or Aspergillus mold and a suitable tablet binder or excipient.

22. The tablet of claim 21 wherein the protease and amylase are derived from Bacillus licheniformis.

23. The tablet of claim 21 wherein the binder is a polyethylene glycol.

24. An effervescent water soluble contact lens cleaning tablet, powder or granule; which comprises an effective concentration of an activator free protease and amylase derived from a Bacillus or Streptomyces bacteria or Aspergillus mold and an effervescent salt, said protease remaining active when in the presence of a chelating agent.

25. The cleaning tablet, powder or granule of claim 24 wherein the protease and amylase are derived from Bacillus licheniformis.