FI62463C - FOERFARANDE FOER KATALYTISK REDUKTION AV VAETEPEROXID I MJUKA MED VAETEPEROXID DESINFICERADE KONTAKTLINSER - Google Patents

Description

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FINLAND I— * FI N LAN D (21) ^ wnttlhukumu · —ft ** nt «n« dki »lng 1937/7 ^ (22) HtkamiipUvi - AiwMutlngadag 25-06.7 ^ (23) Alkupllvl — GUtlghmdag 25.06.7 ^ ( 41) Tullut Julktouksl - Blhrtt offancHg 27.09.75 ***** M * rMmthMHu »(44) ΝΙΜΜΜρ ™» |. month «mm4« m date. -

Patent · och raflstarttjrralMn 7 AnaMcan utlagd oeh utl. * Krtfu «publican * 30.09.82 (32) (33) (31) Pyjrfnttjr atuelkau * —tagird prlorltac 26.03-7 ^ USA. (US) U5U1I + I Toteennäytetty-Styrktitud ) AO, Inc., lU Mechanic Street, Southbridge, Massachusetts, USA (72) Charles Anthony Gaglia, Jr., Flanders, New Jersey, USA (US) (Kol) Oy Kolster Ab (5M Method for catalytic reduction of hydrogen peroxide in soft The present invention relates to a new method for the reduction of hydrogen peroxide in a sterically soft contact lens before it has been placed in the eye before placement in the eye.

Generally, soft contact lenses are made from certain hydrophilic polymers. For example, the soft lens marketed by Bausch & Lomb is a homopolymer of hydroxyethyl methacrylate (HEMA) crosslinked with ethylene glycol methacrylate (EDMA). On the other hand, the soft contact lenses soon marketed by American Optical Corporation consist of a polymer obtained by polymerizing a mixture of HEMA, some EDMA, methacrylic acid, and about 20% poly-N-vinylpyrrolidone (PVP). All lenses made of these materials have clearly hydrophilic properties and are soft and flexible when wet.

Although these lenses are not actually perforated, their molecular porosity allows water, oxygen, and tears to penetrate through the lens structure. In order for these lenses to be cleaned effectively after use, it is important that all contaminants be removed from both the surface of the lens and its interior. Hydrogen peroxide has been reported to effectively kill all microorganisms in contact lenses. As shown in "Soft Contact Lens", CV Mosby Co., St. Louis (1972), p. 247, hydrogen peroxide penetrates the lens in about 30 seconds, oxidizes the mucoprotein on the lens surface and at the same time acts as an effective sterilant for microorganisms in the eye. .

However, prior to placement in the eye, a soft contact lens treated with hydrogen peroxide must be rinsed several times in isotonic, buffered saline to remove residual hydrogen peroxide. The isotonic, buffered saline solution contains 0.85% by weight of sodium chloride, is buffered to pH 6.9-7.1 and contains 0.001% thimerosal and 0.1% disodium edatate as a preservative. In some cases of hypersensitivity, as little hydrogen peroxide as 10-20 ppm (parts per million) may be somewhat irritating to the eye. Today, multiple dissolution and rinsing in isotonic, buffered saline is used, but this does not remove all of the hydrogen peroxide because the rinsing alone serially dilutes the hydrogen peroxide to a lower concentration. The soft contact lens thus rinsed may still contain an irritating amount of hydrogen peroxide.

There are other problems with proper rinsing. One of the main problems is the rather long time and personal care required for proper rinsing. It has been found that proper dissolution and rinsing requires four separate rinses. Given the necessary intermediate leaching, the acceptable treatment takes n.

30 minutes or more. Other disadvantages are that rinsing treatments and cycles are often highly subjective and may vary in potency from person to person. In addition, proper four-rinse treatment requires large amounts of saline, which is cumbersome and inconvenient in practice.

A simple and convenient method has been invented for treating and sterilizing soft contact lenses with hydrogen peroxide and then removing hydrogen peroxide from the soft contact lenses without the necessary, repeated soaking and rinsing steps.

The process of the invention is characterized in that the lenses are contacted simultaneously with or after the disinfection treatment with an aqueous system preferably containing an effective amount of a hydrogen peroxide decomposing catalyst selected from the metals of Group 4, 5 and 6 of the Periodic Table, lanthanides. . Thus, the soft contact lens is effectively sterilized by allowing it to be exposed to hydrogen peroxide for about 10 minutes, however, the treated lens does not need to be removed from the treatment vessel because the accompanying catalyst decomposes the remaining hydrogen peroxide as follows: 2 H 2 O 2 -2 H 2 O + 2/0 / -)

Thus, hydrogen peroxide is removed by converting it into harmless reaction products, i.e. water and oxygen at birth. The latter, of course, acts as an additional sterile. Since the decomposition of hydrogen peroxide to a satisfactory level normally takes about six hours, depending on the amount of catalyst, the treatment area and the geometry of the vessel, and even if the reactions compete with each other, effective sterilization has taken place well before the hydrogen peroxide is almost completely decomposed.

If the hydrogen peroxide solution initially contains 0.85% by weight of sodium chloride, the conversion of hydrogen peroxide to water and oxygen results in an almost isotonic saline solution. Thus, upon decomposition of the hydrogen peroxide, the lens is stored in an almost isotonic saline solution, which very well retains the original optical properties and dimensions of the hydrophilic lens. After removal of the hydrogen peroxide decomposition product, it is rinsed once in isotonic saline, after which placement of the lens in the eye is easy, comfortable, and physiologically acceptable.

Instead of a separate final rinse in isotonic, buffered saline, the buffer system required to buffer the 0.85% sodium chloride solution to the desired pH n can be used.

6.9-7.1, add at the same time as sodium chloride to the hydrogen peroxide solution used for sterilization.

Thus, in a typical embodiment of the invention, a suitable amount of 3% by weight hydrogen peroxide containing sufficient sodium chloride to obtain a 0.85% saline solution is added to a container consisting of a cup, a holder of two sterilizable contact lenses and an effective amount of decomposition metal catalyst. The soft contact lenses are allowed to be in contact with this hydrogen peroxide water system for about six hours. When operating under these conditions, it has been found that the lenses are effectively sterilized and the measurable residual hydrogen peroxide is about 20 ppm, which about 90% of contact lens wearers can tolerate. Contact lenses are completely non-irritated by rinsing in isotonic saline, reducing the hydrogen peroxide content factor to less than 10 ppm.

If the sterilization is carried out in such a way that, after completion of the catalytic decomposition of hydrogen peroxide, the final solution is a 0.85% aqueous solution of sodium chloride buffered to pH 6.9-7.1, it can be added to a 3% by weight hydrogen peroxide solution while adding a sodium chloride buffer system with a suitable combination of monobasic sodium phosphate and dibasic sodium phosphate. Thus, the desired sterilization is performed in a volume of about 10 ml of a 3% by weight aqueous hydrogen peroxide solution. Addition of 90 mg of sodium chloride, 0.72 mg of monobasic sodium phosphate and 6.4 mg of anhydrous dibasic sodium phosphate as a final solution after completion of the catalytic decomposition of hydrogen peroxide gives an isotonic saline buffered to pH 7.0. When buffering to pH 6.9-7.1, it has been found that many contact lens wearers can easily tolerate up to more than 30 ppm hydrogen peroxide.

Other useful buffer systems that provide approximately the same results when buffering to pH 6.9-7.1 include suitable tartrate, succinate and glycine buffers or the McIlph phosphate-citrate buffer described in J. Biol. Chem. 49, 183 (1921).

Of the metals belonging to the above-mentioned classes of the Periodic Table, the following can be advantageously used for the decomposition of hydrogen peroxide: Pt, Pd, Ir, Rh, Re, Au, Ag, Cu, Cr, Os, Co, Fe, Mo, W, Mn, Ce and Th . At their most effective, these catalysts are in a form in which the catalytically effective surface is at its maximum.

Due to their easy availability, platinum, gold and palladium are recommended. The catalyst is usually on the support. For example, platinum black is attached to platinum or other supports, such as alumina, carbon, stainless steel, or another support commonly used as a support for these catalysts.

In practice, the catalyst is usually attached to a vessel in which hydrogen peroxide sterilization is performed. In order to obtain the largest possible surface area, a suitable shape must be chosen for the catalyst support. The support may be an alumina wire, a thin film or a suitably shaped tablet coated with the catalyst itself.

Any inactive support that does not adversely affect the catalyst can also be used as the catalyst support. Complex, molded moldings that can be easily molded from a variety of unreacted thermoplastics and thermosets are highly recommended because the casting provides a relatively large internal surface area relative to the overall external dimensions. These molded moldings are then coated with a catalyst to form the desired active metal catalyst, for example platinum black, on their surfaces. Since catalyst activity is a surface phenomenon, a massive catalyst offers no advantages. In addition, the acquisition and exchange cost of some active metals is an obstacle to the use of a massive catalyst. Thus, forming the widest possible surface of the active catalyst on the inactive support is most economical.

A polymer sold under the trade name "Noryl" by General Electric Company is particularly preferably used as the molded support for the hydrogen peroxide decomposition catalyst. This flux is a phenylene oxide polymer obtained by the oxidative polymerization of 2,6-dimethylphenol, the oxygen-containing intermediate being an amine and a complex of a basic copper salt. These phenylene oxide polymers are described in more detail in U.S. Patents 3,306,874 and 3,306,875.

One of the most readily available and most useful catalysts is platinum black, which can be coated on either thin platinum wires with a diameter of 0.3-1.3 mm or a thin platinum film. The wire or film can then be attached to the inner surface of the container. The container is then ready for use in treating soft contact lenses with hydrogen peroxide and removing hydrogen peroxide from the contact lenses.

One very useful form of platinum black catalyst is a platinum black catalyst on alumina tablets sold by Hengelhard Chemicals Corp., Murray Hill, New Jersey, it contains 0.4% platinum or 0.5% platinum on 3 nm alumina tablets. These 3 mm alumina tablet catalysts are also available coated with 0.5% by weight of palladium, ruthenium or rhodium. They are also sold by Matheson, Goleman & Bell, East Rutherford, New Jersey. Under the trade name "PX 1267", which is a 0.3% by weight platinum-black alumina tablet catalyst, and "PX 1267-1", which is a 0.5% by weight platinum-black alumina tablet catalyst. These alumina tablets have a diameter of about 3 mm and a length of about 3.5-4 mm. One tablet of this catalyst contains about 0.1-0.3 mg of platinum black and is quite well suited for continuous, daily use to decompose a commercially available 3% aqueous hydrogen peroxide solution in an amount of 8-10 ml. It is easy to place one or, preferably, several tablets in a container used for daily hydrogen peroxide sterilization of soft contact lenses. Because these platinum black catalyst tablets retain their efficacy for a very long period of time 6 62463, they only need to be replaced at regular intervals. But because they are readily available at an affordable price, it is recommended to replace them regularly and whenever their potency and activity appear to decrease to ensure full effectiveness. Their activity is readily detectable by observing the formation of oxygen bubbles when the hydrogen peroxide solution is added to a vessel in which soft contact lenses and catalyst are stored and in which sterilization is performed.

The support can be electroplated with a platinum black catalyst as described below. A very convenient and effective way to precipitate platinum black on a support is to cover the support surface with chloroplatinic acid and to reduce chloroplatinic acid to platinum black in a hydrogen atmosphere. Chloroplatinic acid dissolved in a suitable aqueous or organic solvent is sprayed onto a carrier, for example tablets of various shapes, and after evaporation of the solvent, the tablets coated with chloroplatinic acid are placed in a chamber at about 2 kg / cm hydrogen pressure and reduced to platinum black in six hours. Since an elevated reaction temperature is not necessary, the room temperature is completely sufficient in hydrogen reduction.

Although water can be used as a solvent in the preparation of the chloroplatinic acid solution used in the coating, the use of a volatile solvent is recommended for easier volatility. Alcohols, for example methyl, ethyl, propyl, isopropyl, iso-butyl, n-butyl and heptyl alcohols, are likewise suitable as are other conventional solvents, such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate, acetonitrile and 1, 4-dioxane and even isopropylamine.

Solutions containing 0.1 to 1% by weight of chloroplatinic acid are suitable. The amount of chloroplatinic acid to be precipitated on the support is that after reduction the platinum black is about 0.2-0.5 mg / cm.

The support can also be coated with platinum black by coating it with a chloroplatinic acid solution and reducing the chloroplatinic acid by chemical heating. Such a solution is prepared from equal volumes of 5% aqueous chloroplatinic acid, formaldehyde (form silver grade) in 1N aqueous sodium hydroxide solution and 0.5 parts by volume of 1% aqueous sodium carbonate solution. Preferably, the support is preheated to 100 ° C, uniformly coated with the solution described above, and reheated to 100 ° C for about 10 minutes. The method is repeated until the desired amount of platinum black has precipitated on the support. To remove sodium carbonate and sodium hydroxide residues, the coated support is washed in distilled water 62463, dissolved in 1N aqueous hydrochloric acid for about two hours, and washed twice with distilled water.

The following examples illustrate the practice of this invention.

Example A

When platinum black on platinum is used as a catalyst, this is easily obtained by electrolytic deposition on either platinum wire or platinum film. The metal to be coated is connected to the negative terminal of a 3 V DC source and immersed in a solution of 3% platinum chloride and 0.025% lead acetate. Platinum wire can be used as the anode. The power is allowed to run for 30 seconds. The platinum solution is removed and the metal is washed with 1 N sulfuric acid where it is allowed to soak for about a minute. The washings are removed, the metal is placed in the Platinization solution and the electrolysis is continued for another 30 seconds. The platinizing solution is removed and the metal is rinsed with distilled water. Platinum black forms an adhesive, even and complete coating on the surface of the carrier.

When precipitating platinum black on a platinum wire with a diameter of 1.04 mm and a length of 12.7 mm, a platinum black with an area of about 4.97 cm is obtained.

Similarly, platinum black can be deposited on both sides of a 6.35 x 50.8 mm platinum strip by the same electrolysis method, and this strip can also be used as a hydrogen peroxide decomposition catalyst.

Example 1

A 127 mm platinum wire coated with platinum black is placed in a cylindrical vessel with a volume of about 9 ml according to Example A. The wire is helically on the walls of the container and extends from the bottom to about 3.2 mm from the top of the container. Two sterilizable, soft contact lenses are placed in a vessel and about 9 ml of isotonic saline (0.85% sodium chloride) containing 3% hydrogen peroxide is added to the vessel. The initial hydrogen peroxide concentration is about 30,000 ppm and is sufficient to completely sterilize the lenses that come in contact with it in about 10-15 minutes. Catalytic decomposition occurs rapidly. The following table shows the hydrogen peroxide concentration as a function of time.

Hydrogen peroxide concentration (ppm)! After 1 h- 2 h- 4 h- 6 h- 6 h + I one rinse with isotonic saline j_____ solution__ 15650 1 625 315 140 5.9; _j ____ 8 62463

The hydrogen peroxide concentration is determined by Nordschow et al.,

Anal. Chem., 40, 465 (1968).

Example 2

The soft contact lens sterilization procedure described in Example 1 is repeated, but using a 457 mm long and 0.41 mm diameter platinum wire coil coated with platinum black by the electrolysis method described in Example A above as a hydrogen peroxide decomposition catalyst.

The hydroxide concentrations in the three separate tests were as follows:

Hydrogen peroxide concentration (ppm) after 1 h- 2 h- 4 h- 6 h- 6 h + one rinse with _____isotonic saline 470 240 55 13 1.8 930 390 85 20.1 2.1 550 355 112 36.1 4.95

Example 3

The soft contact lens sterilization procedure described in Example 1 was repeated using two 50.8 x 6.35 mm platinum black strips coated with platinum black as the hydrogen peroxide decomposition catalyst, which were placed on the inner wall of the test vessel with only one side exposed. The platinum black coating was formed by the 2 electrolysis methods described above. The exposed area was about 6.45 cm.

The hydrogen peroxide concentrations were as follows:

Hydrogen peroxide concentration (ppm) 1 h- 2 h- | 4 h- 6 h- 6 h + one rinse in isotonic ____ after brine_ 140 [47 4.6 I <1 1 <1

Example 4

The sterile soft contact lens sterilization procedure of Example 1 was repeated using platinum black coated alumina tablets containing 0.3% by weight of platinum black as previously described as a hydrogen peroxide decomposition catalyst. The number of tablets used varied as indicated and the hydrogen peroxide concentrations were determined at the same time intervals as in the previous experiments to give the following concentrations: 9,62463

Hydrogen peroxide concentration (ppm) -----

Catalyst- after 1 h- 2 h- 4 h- 6 h- 6 h + one rinsing tablet in isotonic amount of saline solutions _, ______ sess__ 7 1 350 304 97.8 35.2 1.3 10 1 399 126 32.6 8.7 0.6 12_ 550 1 50.5 1 9.8 1.8 0.2_

It is clear from the above that the rate of decomposition of hydrogen peroxide depends on the available catalyst surface area. Thus, the desired rate and processing time can be obtained by increasing or decreasing the number of catalyst tablets used.

Example 5

Twenty cylindrical tablets of Noryl, 12.7 mm long and 15.9 mm in diameter, with six longitudinal grooves 3.2 mm wide and about 1.6 mm deep in the circumference to increase the surface area were placed in a small tablet coating cup and a cup. rotating at about 40 rpm, it was sprayed with a 0.5 wt% solution of HjPtClgtn (chloroplatinic acid) in ethyl alcohol until all the mobile tablets were moist. Hot air was then blown into the cup until the ethyl alcohol evaporated. The alcoholic solution of chloroplatinic acid was sprayed again into the cup until the tablets were wet and the alcohol was re-evaporated with hot air spray. The procedure was repeated until about 30 ml of solution per 10 cylinders had been sprayed into the coating cup.

The dried chloroplatinic acid coating adhering to the surface of the tablets was then converted to platinum black by reduction with hydrogen gas. The coated tablets were placed in a sealed container at a hydrogen pressure of about 2 kg / cm and kept in this hydrogen atmosphere for about six hours at 20-25 ° C to perform the desired reduction.

Each tablet contains 4.5 mg of platinum black, which corresponds to about 0.2% by weight of the carrier.

The soft contact lens sterilization procedure described in Example 1 was repeated using a platinum black coated tablet prepared above as a hydrogen peroxide disintegration catalyst. Hydrogen peroxy dicon concentrations were determined in each case at the same time intervals as in the previous experiments. Using 10 ml of 3% by weight hydrogen peroxide as sterilant, the following hydrogen peroxide concentrations were obtained: 10 6 2 4 6 3

Hydrogen peroxide concentration (ppm) »-------- f iNumber of catalyst tablets after 1 h -__ 2 h- 4 h- 6 h | I 1 440 151 4104

I I

I 1 615 192 48 16 j! 1 475 148 36 11 j! 1 410 139 39 9 • J._345 115 [26_ | _9__

Example 6

The soft contact lens sterilization procedure described in Example 5 was repeated using 10 ml of 3% by weight hydrogen peroxide supplemented with 90 mg of sodium chloride, 0.72 mg of monobasic sodium phosphate and 6.4 mg of anhydrous sodium dibasic phosphate.

After 5 hours, the hydrogen peroxide concentrations in the five separate experiments were 20, 26, 20, 13, and 19 ppm. The pH was 7.0. After 5 hours, the average residual hydrogen peroxide in the 19 separate experiments was 26 ppm. Examples 7-12 The alumina support in the form of 3 mm diameter tablets was separately coated with palladium, platinum, rhodium and ruthenium in each case in an amount of 0.5% by weight based on the total weight of the catalyst. These catalysts were used in the sterilization of soft contact lenses to decompose hydrogen peroxide by the method described above. In addition, 0.3% by weight of platinum-coated alumina tablets were tested. The results are shown in the following table: Hydrogen peroxide concentration ----- 1--1-

Pre- Kata- Tablet- 1 h- 2 h- 4 h- 6 h * 6 h + marked road rinse rate after ______ 7 bales- 10 2 980 840 134 80 6.2 dium 0.5% 8 rhodium 10 11 900 6 025 1 520 219 31.6 0.5% 9 rute- 10 1 420 380 82 28 2.0 nium 0.5% 10 platinum 10 550 126 33 8.7 ^ 1 0.3% 11 platinum 8 990 190 68 28 <1 0.5% 12 platinum 7,880,130 22 3.2 <.1 0.5%