IL46397A - Process for sterilizing contact lenses - Google Patents

Description

PROCESS FOR STERILIZING MEDICAL OR flURgl lL Ί " BQUIPMBM* CONTA T L·&Nse$ The need for an effective and simple sterilizer system for hydrophilic contact lenses (the so-called soft contact lenses) has become rapidly apparent.

The three methods currently used for sterilization of lenses all have disadvantages: 1. Boiling in saline solution.

This method is very effective against eye pathogens. However, it is inconvenient for the contact lens wearer to carry a boiling device and in fact in one study 16% of those interviewed indicated the boiling cycle might preclude them from purchasing hydrophilic lenses made of hydroxyethylmethacrylate (HEMA) polymers. 2. Treatment with 3% Hydrogen Peroxide.

This method is effective germicidally but can be slow, and also has to be handled properly. The water has to be treated with sodium bicarbonate before insertion of the lenses in the eye. It is a fact that this system has not gained widespread acceptance in practice. Also, very high peroxide concentrations are required to kill certain microorganisms. 3. The use of chemical agents.

Two basic types of isotonic chemical sterilizing solutions are commercially available.

One contains chlorhexidine gluconate as the active component and the other contains chlorhexidine, ethylene diamine tetraacetic acid and thimerosal (sodium (ethylmercuri) thiosalicylate) . Neither chemical system is ideal when prolonged wearing comfort, complete sterility, reliability and allergic response are considered. Although these solutions have been tested for their cleaning efficiency, they fall significantly short of accomplishing this objective when used on a routine basis; see Krezanoski, J. American Op'tometrie Association , Vol. 43, pages 305-307 (1972). Other problems are shown in Phares Patent 3,689,673 and Phares, J. American Optometric Association, Vol. 43, pages 308 et seq. Rankin Patent 3,755,561 also discloses a bactericidal solution for treating contact lenses.

A sterilizing system for hydrophilic contact lenses desirably has all of the following properties: 1. It should be effective against the ^various types of eye pathogens in a suitable exposure time; 2. It should break down into innocuous products; 3. It should not be absorbed into the lenses; 4. It should not affect the lens characteristics ; There has now been found a novel system that achieves these objects. The novel system comprises a hypochlorite solution. The hypochlorite solution is completely bactericidal against four known eye pathogens: Staphylococcus aureus, Eschericia coli; Pseudomonas aeruginosa and Candida albicans in 30 minutes or less. The novel system is thus effective against the microorganisms present.

The hypochlorite does not penetrate into the lens.

Before insertion of the lens into the eye, the surface hypochlorite is rendered inactive with an appropriate reducing agent. Thus, eventual damage to the ocular tissue by hypochlorite is not possible since residual hypochlorite is destroyed.

The breakdown products of the hypochlorite and the reducing agent are harmless.

The final total system is immune to bacterial growth.

The hypochlorite can be any inorganic or organic hypochlorite having the general formula A(OCl)x where A is an inorganic metal or organic group such as alkali metal, e.g. , sodium, potassium and lithium, alkaline earth metal, e.g. barium, magnesium and calcium, alkyl hypochlorites, e.g. t-butyl, t-amyl, ethyl, methyl, propyl, isopryl, etc. and x is the absolute charge on the inorganic or organic Thus according to the present invention there is provided a process for sterilizing contact lens comprising immersing the contact lens in a solution of (1) a source of hypochlorite in an amount effective to kill the pathogenic microorganisms present, the amount of hypochlorite being not over 0.05 percent of the solution, said hypochlorite being non-toxic in the concentration employed and being sufficient to render ineffective eye pathogens within a period of 5 minutes to 3 hours, and thereafter reducing the hypochlorite in the solution to chloride with (2) a non-toxic reducing agent in am amount sufficient to reduce all of the hypochlorite, the solution of (1) plus (2) also containing (3) a non-toxic buffer to maintain the pH at 6.5 - 8.5.

In U.S. Patent 3,755,179 there is described a'· chemical composition comprising a mixture of alkali and/or alkaline earth metal hypochlorites and, as a stabilizing and/or reinforcing agent, alkali and/or alkaline earth metal pyrosulfates .

Similarly in U.S. Patent 3,260 674 there is described a self-supporting composition in the form of a compacted tablet having the ability to evolve oxygen, however neither of said patents teach or suggest the specific and specialized process for sterilizing contact lens according to the present invention. substituent. Thus, there can be used by way of illustration sodium hypochlorite, potassium hypochlorite, lithium hypochlorite, calcium hypochlorite, t-butyl hypochlorite or t-amyl hypochlorite.

In place of adding the hypochlorite as such there can be employed materials which form hypochlorous acid in aqueous solution and which are stable on storage in the dry state. Examples of such materials are Ν,Ν-dichlorotaurine (sodium salt) , Ν,Ν-dichloro beta alanine, Ν,Ν' -dichloroisocyanuric acid (potassium salt), Ν,Ν' -dichloroisocyanuric acid (sodium salt) , N-chorurea, Ν,Ν' -dichloro-2 , 5-piper-azinedione , Ν,Ν' -1 , 3-dichloro-5 , 5-dimethylhydantoin , trichloroisocyanuric acid, N-chlorosuccinamide , Ν,Ν' -dichloroglycocyamine, and N,N-dichloroglycine.

The concentration of the hypochlorite or source thereof is not particularly critical and can vary from 0.05% or less to 2.5% or even 5% or more by weight of the aqueous solution. It will be realized that the minimum effective amount will vary somewhat depending on the hypochlorite source and the bacteria present, e.g., Ν,Ν-dichloroglycine was effective at 0.05% against S . aureus in 1 hour and for E. coli, P. aeruginosa and C. albicans in 5 minutes and at 0.5% concentration it was effective against all four organisms in 5 minutes. The maximum amount of hypochlorite in the solution is controlled simply by economics.

The hypochlorite whether initially present as such or formed in situ from another source thereof has to be reduced to render it innocuous after it has acted to kill any bacteria which may be present.

The reducing agent must have the following qualifications: 1. It must be able to reduct the hypochlorite ion COCl") to the chloride ion CC1~) , that is, the combined half potentials of the hypochlorite and reducing agent must be positive. A large number of widely varying reducing agents meet this qualification as is recognized in the art. 2. The reducing agent itself and its oxidized form (i.e., the reducing agent is oxidized when it acts as a reducing agent) must be non-toxic. Examples of suitable reducing agents include alkali metal and alkaline earth metal thiosulfates , e.g., sodium thiosulfate, potassium thiosulfate, and calcium thiosulfate, ascorbic acid, reducing sugars, e.g. d-glucose, 1-glucose, lactose, maltose, d-fructose, %d-xylose, d-arabinose, etc.; organic and inorganic peroxides, e.g., sodium peroxide, barium peroxide, benzoyl peroxide, peracetic acid, perpriopionic acid.

The reaction between the reducing agent and the hypochlorite can be summarized by the following reaction scheme: 0C1~ + 2ee + H 0 ^F=^ Cl~ + 20R→ ( pK/V 7) 2 \ Q where 2e are su lied b the reducing agent. The amount of reducing agent is not critical so long as sufficient is used to react with all of the hypochlorite.

While the hypochlorite compositions of the invention are preferably employed to sterilize hydro-philic contact lenses they can also be employed to sterilize the more conventional hard contact lenses as well as other metal, glass or plastic medical and dental equipment of all types. Thus there can be sterilized with the hypochlorites, plastic and metal medical (including surgical) equipment and dental equipment such as forceps, intrauterine devices, scalpels, scissors, speculums, dentist drills, picks, clamps, needles, syringes, otoscopes, metal and plastic tongue depressers, dental mirrors, crown removers, catheters, metal mouth presses, plastic and metal components of hearing aid equipment.

It is preferred to employ a buffered pH which is close to neutrality in the reducing agent system. This is particularly true with soft contact lenses. The eye is very sensitive to pH changes and thus a sterilizer system should have a pH in the range of 6.5 - 8.5. Any conventional non-toxic buffer capable of maintaining this pH can be used, e.g. , a mixture of potassium dihydrogen phosphate (0.025 molar) and disodium hydrogen phosphate (0.025 molar) in water or other mixtures of these salts which give a pH in the range. of 6.5 - 8.5 such as those shown in the 6 Handbook of Chemistry and Physics, 47th ed. (119.66) , page D-79, e.g., 0.008695 molar KH PO and 0.03043 molar or other buffer mixtures set forth on the same page which give pH values in the range of 6.5-8.5, e.g., a mixture of 50 ml of 0.25 molar borax and 20.5 ml of 0.1 molar HC1, soidum citrate-citric acid buffers, etc.

Instead of using a buffered hypochlorite, composition alternatively unbuffered hypochlorite can be used and the contact lenses and other surgical or medical equipment often treated, e.g. the equipment can be washed with sterile water to remove any residual hypochlorite solution.

The invention can be employed to sterilize any of the presently known hydrophilic contact lenses, i.e. the soft contact lenses. The hydrophilic lenses are generally polymers of hydroxyalkyl acrylates and methacrylates , e.g., polymers of hydroxyethyl meth-acrylate, hydroxyethyl aerylate, hydroxypropyl methacrylate and hydroxypropyl aerylate. They are normally »polymers of hydroxyethylmethacrylate (HEMA) , usually sparingly crosslinked polymers thereof wherein cross- linking agent is ethylene glycol dimethacrylate, e.g., 0.05-2% of crosslinking agent. However, other cross- linking agents can be present in addition to or in place of ethylene glycol dimethacrylate. Thus, there can be used as crosslinking agents: ethylene glycol dimethacrylate, 1,4-butylene dimethacrylate, diethylene glycol dimethacrylate, propylene glycol dimethacrylate, diethylene glycol dimethacrylate, dipropylene glycol dimethacrylate, diethylene glycol diacrylate, dipropylene glycol diacrylate, divinyl benzene, divinyl toluene, diallyl tartrate, allyl pyruvate, allyl malate, divinyl tartrate, triallyl melamine, Ν,Ν' -methylene bisacryl-amide, diallyl maleate, divinyl ether, diallyl monoethy-lene glycol citrate, ethylene glycol vinyl citrate, allyl vinyl malaata, diallyl itaconate, ethylene glycol diaster of itaconic acid, divinyl sulfone, hexahydro-1 , 3 , 5-triacryltriazine, triallyl phosphite, diallyl ether of benzene phosphonic acid, polyester of maleic anhydride with triethylene glycol, diallyl aconitate, divinyl cintraconate, diallyl fumarate, glycidyl methacrylate , glycidyl acrylate, allyl acrylate and allyl methacrylate.

The compositions and procedures of the invention can also be used to sterilize contact lenses wherein HEMA is copolymerized (usually in the presence of 0.05%-2% of a crosslinking agent), with vinyl *pyrrolidone, acrylamide, methacrylamide, methoxyethoxy-methacrylate, methoxytriethylene glycol acrylate or methoxytriethylene glycol methacrylate or wherein HEMA is polymerized or copolymerized in the presence of polyvinyl pyrrolidone, vinyl pyrrolidone-vinyl acetate copolymer or other vinyl lactam polymers.

Thus, the invention can be employed to sterilize hydrophilic contact lenses made in accordance with or disclosed in ichterle Patent 2,976,576; Wichterle Reissure Patent 27,401; Wichterle Patent 3,361,858; ; Wichterle Patent 3,476,499, Isen Patent 3,488,111; Wichterle Patent 3,496,254; Wichterle Patent 3,499,862; Shepherd Patent 3,618,213; Wichterle Patent 3; 542, 907; Wichterle Patent 3,557,761; Leeds Patent 3,621,079; Wichterle Patent 3,660,545 Wichterle Patent 3,679,504; Stoy Patent 3,691,263; Wichterle Patent 3,699,089; Steckler Patent 3,532,679; Seiderman Patent 3,639,524; Seiderman Patent 3,503,942; Seiderman Patent 3,721,657; Ewell Patent 3,647,736; O'Drascoll Patent, 3,700,761; Stamberger Patent 3,758,448} and Stamberger Patent 3,772,235. The entire disclosures of the patents mentioned in this paragraph are hereby incorporated by reference. - The combination of medical or dental equipment sterilizer solution containing hypochlorite with subsequent addition of neutralizing agent is unique in that among others the killing ' capacity is fast and completely effective but the hypochlorite does not penetrate the lens and damage to the ocular tissue cannot occu .

The sterilizer system is preferably a two componant system comprising a source of non-toxic hypochlorite as one componant and a non-toxic reagent capable of reducing the hypochlorite source to chloride as the second componant. The sterilizer system can be formulated in solution form i.e. one solution containing hypochlorite and another solution containing the reducing agent or in solid form, i.e. two componant tablet or capsule form, two separate tablets or capsules , one containing the hypochlorite and the other the reducing agent, or preferably the sterilizing system can be a two package system in which the first package is in solution form, e.g., in a bottle, squeeze container, etc. the solution of reducing agent can be applied from a squeeze bottle when the hypochlorite is applied either as a tablet or solution. The most appropriate form is a two component tablet, one layer containing the hypochlorite and if desired, the buffer ingredient which dissolve instantly to kill eye pathogens, and the other layer, e.g., either a core layer containing the reducing agent or a bottom layer, which dissolves after the bactericidal action of the hypochlorite is complete and reduces the hypochlorite to CI*". Thus, any of the conventional water sensitive protective coatings can surround the reducing agent. The water sensitive coating should be sufficiently thick to provide protection for the reducing agent for sufficient time for the hypochlorite to act as a sterilizer.

Unless otherwise indicated all parts and percentages are by weight.

EXAMPLE 1 In this example, there were employed two *solutions for sterilization, one of which contained the hypochlorite in an aqueous solution buffered close to neutrality and the other contained the reducing agent in a stoichiometric excess of the hypochlorite in an aqueous solution which was also buffered close to neutrality. 10 A 50 ppm. solution of NaOCl in water was prepared by dilution of stock 5% NaOCl solution. The diluted solution was buffered to a pH of 7.4 with a KH PO -Na HPO, buffer (approximately 0.008695 molar 2 4 2 4 ^ .

KH2P04 and °-03043 m°lar a2HP04). After the hydro-philic contact lenses (made of hydroxyethyl methacrylate polymer available commercially as Soflens) were exposed to the 50 ppm NaOCl dilution for 30 minutes (this can 1 be increased to k hour, 3 hours or even longer if desired, e.g., overnight, and can also be reduced to 25, 20, 15, 10 or 5 minutes provided all the bacteria are killed) lOcc. of a 400 ppm Na SO solution buffered at ^ 3 pH 7.4 with KH PO -Na HPO was added to destroy the 2 2 4 active chlorine. The lenses were then ready to be inserted into the eye.

EXAMPLE 2 A two pellet system was used. One pellet contained lithium hypochlorite and ^PO^- a^PO^ buffer so that when the tablet was dissolved in water, the ^composition was close to neutral (about pH 7.3).. The other tablet comprised the caudciag agent, e.g. sodium thiosulfate. The first tablet was dissolved in water to give a solution buffered close to neutrality (pH 7.3), and containing 0.5% lithium hypochlorite. After about 30 minutes there was added the other tablet which contained sodium thiosulfate in a molar amount equal to at least 0.75 moles per mole of lithium hypochlorite in the solution. This destroyed all of the hypochlorite present. The soft contact lens (made from a hydroxy-ethylmethacrylate polymer available commercially as Soflens) could then be removed from the solution and was ready for use. In place of the sodium thiosulfate an equivalent amount of ascorbic acid or glucose can be used.

EXAMPLE 3 A two component tablet was prepared such .that the top layer contained the pelletable hypochlorite (lithium hypochlorite) and buffer ingredients Ki^PO^- a^PO^) to give a solution of hypochlorite having a pH of 7.4 when dissolved in water. The hypochlorite and buffer dissolved as soon as the tablet was placed in water. The soft contact lens (Soflens) was immersed in the solution. The bottom ¾layer of the tablet contained sodium thiosulfate surrounded by gelatin.

After the gelatin had disintegrated, which took about 30 minutes, the sodium thiosulfate dissolved to reduce the active hypochlorite to CI , and render the lens safe for use.

EXAMPLE 4 An alternative two component capsule was prepared by encapsulating the sodium thiosulfate in a layer, e.g. , 6 mil thick, of hydroxyethyl methacrylat ethylene glycol methacrylate copolymer CIO0:0.2) and then having an outer layer of lithium hypochlorite KHoP0 -Na„HPO . When the capsule was placed in water 2 4 2 4 the sodium hypochlorite and buffers dissolved instantly The water leaches through the hydrophxlxc HEMA polymer layer to reach the sodium thiosulfate which is then gradually leached out to reduce the hypochlorite to Cl"~. The two component capsule was placed in water and used to sterilize a hydrophxlxc contact lens (Soflens) in a manner similar to Example 3. In place of sodium thiosulfate there can be used ascorbic acid or lactose, for example. The thickness of the HEMA polymer layer determines the rate of elution of the reducing agent.

EXAMPLE 5 The procedure of Example 2 was repeated but instead of sterilizing contact lenses there was sterilized a stainless stell forceps which had been contaminated with S. dureus.

In similar manner there can be sterilized any other medical or surgical equipment.

In place of sodium or lithium hypochlorite there can be used other hypochlorite sources such as Ν,Ν'Ν''-trichloroisocyanuric acid or 1 , 3-dichloro-5 , 5-dimethylhydantoin, for example. If it is desired to protect the hypochlorite source from the atmosphere until use there can be provided an external protective coating of methyl cellulose, sucrose or other inert water soluble material. The tablets having the reducing agent core surrounded by a hydrophilic polymer which in turn is surrounded by the hypochlorite source and buffer with or without a further outer coating of inert material can be prepared in the manner described in Shepherd Patent 3,577,512 or Gould Patent 3,641,-237 for example. The entire disclosures of these two patents are hereby incorporated by reference.

As indicated , supra , the two component tablet or capsule is preferred since the contact lens wearer is not confronted with a plurality of solutions before his lenses are suitable for insertion, he is not confronted with stability problems encountered with ♦solutions of sources hypochlorite and he need not worry about subsequently adding the reducing agent tablet when employing a two tablet system.

As used in the claims the term tablet is intended to also cover the terms capsules and pills.

Claims (3)

46397/2 WHAT IS CLAIMED IS:

1. A process for sterilizing contact lens comprising immersing the contact lens in a solution of (1) a source of hypochlorite in an amount effective to kill the pathogenic microorganisms present, the amount of hypochlorite being not over 0.05 percent of the solution, said hypochlorite being non-toxic in the concentration employed and being sufficient to render ineffective eye pathogens within a period of 5 minutes to 3 hours, and thereafter reducing the hypochlorite in the solution to chloride with (2) a non-toxic reducing agent in an amount sufficient to reduce all of the hypochlorite, the solution of (1) plus (2) also containing (3) a non-toxic buffer to maintain the pH at 6.5 - 8.5.

2. A process according to' claim 1 wherein the reducing agent is ascorbic acid..

3. A process according to claim 1 wherein the reducing agent is an alkali metal or alkaline earth metal thiosulfate.