DK141956B - Process for Catalytic Reduction of Hydrogen Peroxide in Soft Contact Lenses Disinfected Herewith. - Google Patents

Description

(11) PUBLICATION MANAGEMENT 1956 (imj DENMARK isn int.ci.3 a ei l 2/16 // bsn 11 ^ 00 (21) Arvegnirtg No. 4 ^ 89/74 (22) Filed on 16 »EU 1974 (23) Life day 16 EU 1974 (44) The note presented and submitted to the public on 28 · Jul. 1 980

Dl THE RECTORATE FOR

PATENT AND TRADE MARKET (30) Priority requested from it

Mar 26 1974, 4s4l4l, US

(71) WARNER-LAMBERT COMPANY, 201 Tabor Road, Morris Plains, New Jersey DY950, US.

(72) Inventor: Charles Anthony Gaglia Jr., 5 Mildred Terrace, Flanders,

New Jersey, US.

(74) FuWnrwegtig in the proceedings:

The engineering company Budde, Schou & Co.

(64) Method for Catalytic Reduction of Hydrogen Peroxide in Soft = The Contact Lenses Disinfected Herewith.

The present invention relates to a method for catalytically reducing hydrogen peroxide in soft contact lenses disinfected therewith. In particular, the method of the invention aims at treating the disinfected soft contact lenses before re-applying them to avoid the mucosal irritation which has hitherto been a major reason why many people have not yet become accustomed to wearing the lenses constantly.

Soft contact lenses are generally prepared from certain hydrophilic polymers. Eg. There are soft lenses made from a homopolymer of hydroxyethyl methaerylate (HEMA) cross-linked with ethylene glycol dimethacrylate (EDMA). Furthermore, soft contact lenses known from a polymer obtained by polymerization of a mixture of HEMA with some EDMA, methacrylic acid and ca. 20% poly (N-vinylpyrrolidone) also called PVP. All the lenses made from these materials exhibit pronounced hydrophilic properties and are wet and flexible in wet conditions.

Although these lenses are not exactly pierced or perforated, they do have a sufficient degree of molecular porosity to allow water, oxygen and tear fluid to permeate the entire structure of the lens. In order to effectively clean and disinfect these lenses after wearing them, it is important that all contaminants are removed from both surfaces as well as from the interior of the lens. Hydrogen peroxide has been reported to be an effective agent for treating contact lenses for the purpose of killing any contaminating microorganisms. As stated in "Soft Contact Lens" published by the C.V. Mosby Co., St. Louis (1972) page 247 penetrates the hydrogen peroxide lens over approx. 30 seconds, it oxidizes any mucoprotein found on the lens surface and is also an effective disinfectant against any microorganisms present in the eye.

However, before the soft contact lenses thus treated with hydrogen peroxide can be reinserted into the eye, they must be rinsed repeatedly in isotonic buffered saline, namely to remove any remaining unreacted hydrogen peroxide. Isotonic buffered saline is a 0.85% by weight solution of sodium chloride buffered to a pH of 6.9-7.1 and preserved with 0.001% "Thimerosal" (registered here) and 0.1% disodium ethylenediamine tetraacetate. Hydrogen peroxide, even in small amounts such as 10 to 20 ppm (parts per million) can cause some eye irritation in cases of particular sensitivity. Repeated immersion and rinsing in isotonic buffered saline, as currently practiced, do not always effectively remove all hydrogen peroxide present, because flushing merely works by diluting the hydrogen peroxide to a lower concentration. As a result, the peeled soft contact lens may still retain or retain a sufficient concentration of hydrogen peroxide to be irritating to the wearer.

Appropriate or adequate rinsing also presents other problems. One of the main problems is that a considerable period of time is required and. personal attention and monitoring to carry out an appropriate flushing procedure. To an appropriate, appropriate 4: Γ ..

Or the required leaching and flushing sequence, it has been found that four separate flushes are required. Therefore, with the necessary in between these interposed leaching, an acceptable procedure will take approx. 30 minutes or more. Another disadvantage is that the flushing procedures and sequences are generally highly subjective and lack reproducibility as they can vary widely in efficiency from one person to another. In addition, large volumes of saline solution are necessary to carry out an appropriate procedure with 4-step rinsing, making this practice cumbersome and inconvenient.

In a report on a lecture, held at a contact lens seminar at Ohio State University, J.L. Bitonte et al. in "Symposium on the flexible lens" published by the C.V. Mosby Company Saint Louis 1972, for the problems of sterilizing contact lenses with peroxides and recommends the use of an aqueous 3% hydrogen peroxide solution. Furthermore, it is mentioned that it becomes unstable by the addition of powdered sodium bicarbonate after the hydrogen peroxide has worked for a sufficient period of time or the hydrogen peroxide solution is discarded and replaced with a sodium bicarbonate solution. This neutralizes the acidic pH which the hydrogen peroxide solution produces and which is harmful to the eye. Once soaked in the sodium bicarbonate solution for a sufficiently long period, the lenses are transferred to a fresh saline solution.

However, it has been shown by experimental testing that the above treatment has no effect. There is no significant degradation of hydrogen peroxide (at pH 8.0}, even after 6 hours at 22 ° C where the concentration has only dropped from 3.0 to 2.93% in one case and in another case is still 3 , 0%.

It has now been found that the above desire can be realized by a simple and convenient method of treating soft contact lenses which are disinfected with hydrogen peroxide, so that the hydrogen peroxide, after effecting removal or its residual concentration, is effectively reduced in the soft contact lenses. It is noteworthy that this is accomplished without the repeated soaking and rinsing steps previously considered necessary for efficient elimination of the hydrogen peroxide.

This object is achieved by a method of the kind mentioned in the preamble, characterized in that the lenses are brought into contact with an aqueous system simultaneously with or after the disinfection treatment containing a preferably catalytically effective amount of a hydrogen peroxide decomposition catalyst. selected from metals from periods 4, 5 and 6 of the periodic system, including the lanthanides.

The soft contact lens is hereby effectively disinfected as it should only be exposed to the effect of hydrogen peroxide for a short period of approx. 10 minutes, whereas hydrogen peroxide decomposition takes a long time. Therefore, the lens does not need to be removed from the container in which the disinfection has been carried out, since the co-catalyst present will, after a prolonged period, have such a strong effect on the decomposition of the residue that it is converted into the harmless reaction products water and oxygen in status, nascendi, viz. according to the following reaction terms: 2H2O2 -> 2H2O + 2 [O] -y-02 + 2H2O

The latter, of course, has a further sterilizing effect, which is beneficial but not essential. Although the respective reactions are competing reactions, effective sterilization will nevertheless have taken place to the extent necessary before significant decomposition of H 2 O 2 has occurred, since under normal conditions the decomposition reaction requires approx. 6 hours to reduce H 2 O 2 to a satisfactory low level, depending on the nature of the amount of catalyst, the reactive surface and the geometry of the container.

Initially, if the hydrogen peroxide solution is prepared to contain 0.85% by weight sodium chloride, the final conversion of HgQ 2 to water and oxygen provides a roughly isotonic saline solution as the final product. As a result, once the decomposition of HgCl3 is complete, the lens will be effectively stored in the substantially isotonic saline solution, which is a highly desirable medium for preserving the original optical and dimensional parameters of the lens. A single final rinse in isotonic saline solution after depletion of the H 2 O 2 decomposition product makes the subsequent insertion of the lens easy, convenient and physiologically acceptable.

Instead of conducting a separate final rinse in isotonic buffered saline, the necessary buffer system required to buffer the 0.85 $ aqueous sodium chloride solution to the desired pH of about 6.9-7.1, is added together with the sodium chloride when added to the H2 (S) solution used for sterilization.

141956 5

Thus, in a typical application of the process of the invention, a suitable amount of 3 wt% hydrogen peroxide containing sufficient sodium chloride is provided or introduced to produce a 0.85% saline solution in a container comprising a beaker, a holder with a pair of contact lenses to be sterilized, and an effective amount of the desired decomposition metal catalyst. The soft contact lenses are then allowed to remain in contact with the aqueous hydrogen peroxide system for approx. 6 hours. It has been found that the lenses are thus effectively sterilized and at the same time the residual level of detectable hydrogen peroxide after the application of this method is reduced to approx. 20 ppm, a level acceptable for approx. 90% of contact lens wearers. To avoid any possible irritation in the remaining 10% of the carriers, a single rinse in isotonic saline is recommended as sufficient to reduce the hydrogen peroxide level below 10 ppm, a sufficiently low level to avoid irritation in all, even the most sensitive.

If the sterilization is to be carried out so that the final solution, after the catalytic decomposition of H 2, is completed, a 0.85 # aqueous solution of sodium chloride is buffered to a pH of 6.9 to 7.1, a buffer system comprising an appropriate combination of monobasic sodium phosphate and dibasic sodium phosphate is included when the sodium chloride is added to the 3% by weight hydrogen peroxide solution. For example, thus, the desired sterilization is carried out with a volume of approx. 10 cnP 3 wt% aqueous hydrogen peroxide, addition of 90 mg sodium chloride together with 0.72 mg monobasic sodium phosphate and 6.4 mg anhydrous dibasic sodium phosphate will give an isotonic saline solution buffered to a pH of 7.0 as the residual solution after catalytic decomposition of present HgQjhar occurred. Thus, when the working solution is buffered to a pH of 6.9 to 7.1, it has been found that an HgQ 2 level of even above 30 ppm can be easily tolerated by many contact lens wearers.

Other satisfactory buffer systems which can be used which give substantially equivalent results in buffering to a pH of 6.9-7.1, appropriate tartrate, succinate and glycine buffers or Maclvaines phosphate citrate buffer as described in J. Biol.

Chem. 49, 183 (1921).

Among the metal catalysts for decomposition of hydrogen peroxide belonging to the above classification in the periodic system, the following may be used: Pt, Pd, Ir, Rh, Re, Au, Ag, Cu, Cr, Os, Co, Fe, 141956 6

Mo, W, Μη, Ce and Th. These catalysts are most effective in a form that provides the maximum surface for catalytic activity.

Platinum, gold or palladium are generally preferred because they are readily available. The catalysts are usually supported on a support when used. Eg. platinum may be mounted on platinum or other supports such as alumina, carbon, stainless steel or any other support commonly used as catalyst support for these catalysts. In practice, the catalyst is usually attached to the container in which the hydrogen peroxide sterilization process is carried out. In order to provide the widest possible surface area, it is desirable to provide an appropriately designed support for the catalyst. This support may be in the form of a wire, a thin film or an appropriately shaped pillar of alumina on which the catalyst itself is deposited.

Any other inert support material which has no detrimental effect on the catalyst can also be used as a support or support for the catalyst. Intricate molds or shapes that can be easily molded from many different inert thermoplastic or thermosetting materials are highly desirable as they can be molded to provide a relatively large inner surface relative to their total outside dimensions. These molded forms can then be coated with the catalyst to form the desired active metal catalyst such as platinum black on their surfaces. Since the catalytic activity is a surface phenomenon, there is no advantage in having the catalyst in solid form. In fact, in the case of some expensive active metals, both the acquisition cost at first and later costs of replacement or replacement will be prohibitive. Thus, it is most economically feasible to provide the largest possible surface of active catalyst on an inert carrier.

Of particular interest as a molded substrate for the hydrogen peroxide decomposition catalyst is the polymeric material marketed under the trade name "Noryl" by the General Electric Company.

This plastic material is a phenylene oxide polymer formed by the oxidative polymerization of 2, β-dimethylphenol in the presence of an amine-basic cupric salt complex as the oxygen-bearing intermediate. These phenylene oxide polymers are described in more detail in U.S. Patent Nos. 3 * 306.87¾ and 3,306,875 * 7 141958

An easily accessible, very active and fairly inexpensive catalyst is platinum black, which may be supported on platinum in the form of thin wire, e.g. with a diameter of 0.25 to 1.25 mm, or of platinum foil.

The wire or foil can be easily attached to the inner surface of the container which is then ready for use in the practice of the method. Therefore, according to the invention, it is preferred that the catalyst is platinum black supported on a platinum support in the form of a wire or foil.

Another convenient form of catalyst suitable for use in the process of the invention is platinum black supported on an alumina support in the form of a pill, tablet or granule, hereinafter called a pellet. Such pellets are already commercially available, e.g. equipped with 0.3% platinum black or 0.5% platinum black mounted on 3 mm diameter alumina pellets. These pellets are easy to assemble and extremely active. Similarly, such alumina carriers are impregnated with e.g. 0.5% by weight of either palladium, ruthenium or rhodium. These impregnated 3 mm alumina pellets are e.g. available from Matheson, Coleman & Bell,

East Rutherford, New Jersey, OSA as a "PX 1267" catalyst which is a 0.3% by weight of platinum on alumina in pellet form or as "PX 1267-1" which is a 0.5% by weight platinum on alumina in pellet form. These alumina pellets have a diameter of approx.

3 mm and a length varying from approx. 3.5 to approx. 4.0 mm. A single pellet of this catalyst carries from ca. 0.1 to approx. 0.3 mg platinum black and is quite suitable for continued daily use as a catalyst for the decomposition of commercially available 3% aqueous hydrogen peroxide solutions used in an amount of 8 to 10 cm. Conveniently, one or more of these pellets may be placed in a storage container used for carrying out the daily sterilization of soft contact lenses with hydrogen peroxide. Since these platinum black catalyst pellets remain very effective for a considerable period of time, they need only be replaced at periodic intervals. However, as they are readily available at moderate prices, it is recommended for complete assurance that they are replaced periodically and, moreover, always when their efficiency and activity appear to decline.

Their activity can be easily controlled by visually observing the generation of oxygen bubbles when the hydrogen peroxide solution is added to the container in which the soft contact lenses and catalyst are stored and in which the sterilization is carried out.

141956 8

While the platinum black catalyst can be applied to the substrate by electrolytic deposition as described below, a very convenient and highly effective method of depositing a platinum black coating on the substrate is to cover the substrate's surfaces with chloroplatinic acid and then reduce the ehloroplatinic acid to platinum black in a hydrogen atmosphere. A solution of ehloroplatinic acid in any convenient aqueous or organic solvent may be sprayed onto the substrate, e.g. may be present as differently shaped pellets, and after the solvent has evaporated, the red chloroplatinic acid is placed on the surface treated pellets in a chamber under hydrogen pressure of approx. 2 atmospheres, and reduction to platinum black ends to approx. 6 hours. Since elevated reaction temperatures are not necessary, it is quite satisfactory to use room temperature for the reduction with hydrogen.

However, although water can be used as the solvent for the chloroplatinic acid in preparing the ehloroplatinic acid solution for the coating step, the use of a volatile solvent is preferable, as it can be more easily evaporated. Alcohols such as methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, isobutyl alcohol, n-butyl alcohol and heptyl alcohol are satisfactory solvents, as are other common solvents such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate and ethyl acetate, ethyl acetate and ethyl acetate. .

Solutions containing 0.1 to 1% by weight of ehloroplatinic acid may conveniently be used. Adequate ehloroplatinic acid should be deposited on the substrate to give a platinum coating of from about * 0.2 to about 0.2m. 0.5 mg per cm after reduction.

The substrate or substrate can also be coated with platinum black by first coating with a solution of ehloroplatinic acid, which upon heating will chemically reduce ehloroplatinic acid to platinum black. Such a solution is made of equal volumes of aqueous 5% ehloroplatinic acid, formaldehyde, ethanol, 1N aqueous sodium hydroxide and 0.5 volumes of aqueous sodium carbonate. The substrate is preferably preheated to 100 ° C, then uniformly coated with the above solution, and then heated again to 100 ° C for approx. 10 minutes. The process is repeated until the desired amount of platinum black is deposited on the substrate. To remove any residual sodium carbonate and sodium hydroxide, the coated substrate is washed in distilled water, soaked for 2 hours in 1 N aqueous hydrochloric acid, and then washed twice with distilled water.

The following examples serve to further elucidate the process of the invention.

141956 9

Example A

Where platinum black or platinum is used as the catalyst, it can easily be obtained by electrolytic deposition on either platinum wire or platinum foil. The metal to be coated is connected to the negative pole of a 5 volt DC power source and then immersed in a solution of J>% platinum chloride containing 0.025% lead acetate. A piece of platinum wire is attached to the positive pole of the DC source and serves as an anode. Power is allowed to run for 5 ° seconds. The platinization solution is removed and the metal is washed with 1N hydrochloric acid and allowed to soak in the wash solution for approx. 1 minute. The wash solution is poured off, the platinization solution is placed again around the metal and the stream is allowed to run for another 30 seconds. The platinization solution is removed and the metal is rinsed with distilled water. Platinum black forms a cohesive, well-adhered, uniform and complete coating on the surface of the carrier.

Platinum black deposited on a platinum wire with a diameter of 1 mm and 2 a length of 12.5 cm presents a surface of platinum black of approx. 5 cm.

Similarly, platinum black can be deposited on both surfaces of a strip of platinum foil having a width of 6 mm and a length of 5 cm by the same electrolytic deposition method, and the strip thus coated with platinum black can also serve as a catalyst for the decomposition of hydrogen peroxide.

Example 1.

In a cylindrical container with a volume of approx. 9 cm 2, the 12.5 cm long platinum wire made as shown in Example A is coated with platinum black. The wire is wound so that it fits against the inside wall of the beaker, running like a spiral from the bottom of the beaker to approx. 5 mm from its top. A pair of soft contact lenses to be sterilized are then placed in the beaker, and approx. 9 ml of tear fluid isotonic saline (0.85% sodium chloride) containing 3% hydrogen peroxide are added. Initially, the hydrogen peroxide concentration is approx.

30,000 ppm and sufficient to thoroughly sterilize the lenses after exposure to this hydrogen peroxide solution for approx. 10 to 15 minutes ter. Catalytic decomposition takes place rapidly, with the concentration of H2C> 2 as a function of time given in the table below: ίο 141956

HgO₂j concentration (ppm) after 6 hours + 1 rinse after 1 hour after 2 hours after 4 hours after 6 hours in isotonic __ _ _ __ saline_ 5650 1625 515 140 5.9

The hydrogen peroxide concentration is determined by that of Nordschow, et al * in Anal »Chem. 40, 465 (1968).

Example 2 ♦

The method of sterilizing soft contact lenses described in Example 1 is repeated again, but the hydrogen peroxide decomposition catalyst used in this process is a 46 cm long spiral wound platinum wire 0.4 mm in diameter previously coated with platinum black by the above The electrolytic process described in ExampleA.

The hydrogen peroxide levels determined by the above test method according to Nordschows at the intervals given below in three separate experiments are as follows:

Ho09 concentrate (ppm) - After 6 hours + 1 rinse

After 1 hour After 2 hours After-4 hours After 6 hours in isotonic __ _ _ _ saline_ 470 240 55 15 1.8 950 590 85 20.1 2.1 550 555 112 36.1 4.96

Example 3

The procedure described in Example 1 for sterilizing soft contact lenses is repeated using a hydrogen peroxide decomposition catalyst having a length of 5 cm and a width of 6 mm made of platinum foil coated with platinum black applied to the inner face of the sample cup so that only one surface of the platinum strip is exposed. The platinum coating is made by the electrolytic process described above. The exposed 2 catalyst surface area is ea. 6.5 cm.

The hydrogen peroxide levels are best measured by the North Chows method at the intervals given below and are as follows.

Hg and cone concentration (ppm) ---—-- After 6 hours +1 rinse-

After 1 hour After 2 hours After 4 hours After 6 hours in isoto- _ _ - ________ niak saline 140 47 4.6. <1

Example 4

The method of sterilizing soft contact lenses described in Example 1 is repeated using a catalyst for decomposing hydrogen peroxide in the form of platinum black coated alumina pellets as described above. These carry 0.3 weight percent platinum black. Thus, the number of pellets used varies as indicated in the table below, with the hydrogen peroxide levels determined in each case according to Nordschow at the same intervals as in the previous samples, and the following concentrations are found:

HpOp concentration (ppm).

Catalyst After 6 hours + 1 flush pellets After After After in isotonic saline number 1 hour 2 hours 4 hours 6 hours _____ 7 3150 504 97.8 55.2 1, 5 10 1599 126 52.6 8.7 0.6 12 550 50.5 9.8 1.8 0.2

From the above results, it is clear that the rate of decomposition of the hydrogen peroxide is dependent on the catalyst area provided. Accordingly, any desired rate can be obtained and the desired treatment period determined by increasing or decreasing the number of catalyst pellets used.

141956 12

Example 5

Twenty cylindrical pellets having a length of 1.25 cm and a diameter of 1.6 cm are provided with six along the circumference, spaced vertically 3 mm wide and ea. 1.5 mm deep recesses or grooves to provide extra surface area and made of "Noryl" are inserted into a small tablet coating pan, while the pan rotates with ea. 40 rpm per minute, a 0.5% by weight solution of HgPtClg (Chiprplatinic acid) in ethyl alcohol is sprayed into the pan until all the moving pellets are wet. Then, warm air is blown into the pan until all the ethyl alcohol has evaporated. Alcoholic ehloroplatinic acid solution is again sprayed into the pan until all pellets are moistened and alcohol is evaporated again using a stream of hot air. The procedure is repeated until injected ea. 10 cnP solution for every ten cylinders present in the coating pan.

The dried chloroplatinic acid coating on the surface of these pellets is then converted to platinum black by reduction with gaseous hydrogen. The coated pellets are placed in a closed container under pressure. 2 atm. hydrogen and is kept under this hydrogen atmosphere for approx. 6 hours at a temperature of 20 to 25 ° C to effect the desired reduction.

Each pellet carries a weight amount of platinum of approx. 4.5 mg, which is equivalent to approx. 0.2% by weight of the base material.

The method of sterilizing soft contact lenses described in Example 1 is repeated using the catalyst thus produced. According to Nordshow, the hydrogen peroxide levels are determined in each case at the same intervals as for the above 3 samples. Using 10 cm 3% by weight of hydrogen peroxide as the sterilizing medium, the following 3 C concentrations are found at the indicated intervals.

• · <141956 13

Hg And Wife a t ra t i on (ppm)

Catalyst pills number After 1 hour After 2 hours After 4 hours After 6 hours 1 440 151 -41 14.

1 615 192 48 16 1 4-75 14-8 36 11 1 410 139 59 9 1 345 115 26 9

Example 6

The procedure described in Example 5 for sterilizing 3 soft contact lenses is repeated using 10 cm 3 weight percent hydrogen peroxide, to which is added 50 mg sodium chloride, 0.72 mg monobasic sodium phosphate and 6.4 mg anhydrous dibasic sodium phosphate. The H 2 O 2 concentrations found after 5 hours for each of five separate samples are 20 ppm, 26 ppm, 20 ppm, 13 ppm and 19 ppm, respectively. The pH is 7.0. 19 separate disinfections are performed with H 2 O 2 decomposition. The average residue is H 2 O 2 after 5 hours thereby proving to be 26 ppm.

Examples 7-12

An alumina carrier in the form of pellets having a diameter of approx. 3 mm are coated with palladium, platinum, rhodium and ruthenium respectively in an amount of 0.5%, based on the total weight of the catalyst. These catalysts are used to decompose hydrogen peroxide in soft contact lenses after disinfecting the lenses with an aseptic solution following the above procedure. Aluminum oxide pellets with diameter approx. 3 mm impregnated with 0.3% platinum as coating. The test results obtained are given in the table below: 14 1A19 5 6

Number of residual peroxide (ppm) after_

Ex. Catalyst Pellets 1 hour 2 hours 4 hours 6 hours rinse 7 Palladium Q, 5% 10 2980 840 134 80 6.2 8 Rhodium 0.5% 10 11900 6025 1520 219 31.6 9 Ruthenium 0.5% 10 1420 380 82 28 2.0 10 Platinum 0.3% 10 550 126 33 8.7 <1 11 Platinum 0.5% 8 990 190 68 28 <1 12 Platinum 0.5% 7 880 130 22 3.2 <1