ENZYME CONTAINING COMPOSITION FOR CLEANING CONTACT LENSES AND METHOD THEREFOR

Abstract: The invention concerns a composition including a core with a catalytic substance for decomposition of hydrogen peroxide to oxygen and water. The composition is characterized by that the core is surrounded by a membrane, which is expandable in aqueous medium and which comprises of a water insoluble polymer and a water soluble porecreating substance, which is randomly distributed in the polymer, whereby the membrane permeability for the catalitic substance increases concurrently with the expansion of the membrane in the aqueous medium.

Description: ENZYME CONTAINING COMPOSITION FOR CLEANING CONTACT LENSES AND METHOD THEREFORE. Background Disinfection of contact lenses is mainly carried out by treat¬ ing the lenses once a day (or up to once a week) with an aqueous hydrogen peroxide (3 %) solution. The killing effect depends on the concentration of the hydrogen peroxide solu- tion and the time during which the lenses are in contact with the solution. Minimum 1,5 % during minimum 20 minutes is regarded to give a sufficiently killing effect. After the disinfection is completed all hydrogen peroxide must be removed from the lenses in order to avoid that the cornea is damaged. Even as low concentrations of peroxide as 10 pp or less in the lenses can cause severe damages. The removal of the hydrogen peroxide can be carried out in different ways. The-most common way is the use of platinum as a catalyst for the decomposition of hydrogen peroxide and the use of the enzyme catalase for the same purpose. The method based on platinum is carried out in such a way that a plate of platinum is mounted on the bottom of the di¬ sinfection vessel. When the solution of hydrogen peroxide is added the decomposition process starts immediately. Each plate of platinum is intended for three months daily use. A new plate gives a rapid decomposition process, which can je- opardize the killing effect, whereas a plate, which has been used for some time, gives a remarkably reduced decomposition effect with big risk for remaining high concentrations of hydrogen peroxide after the recommended treating time, 6 h. Accordingly the risk of damages on the eye is big. The advantage of the method with the decomposition with pla¬ tinum is that it is regarded as easy to use by the user be¬ cause disinfection and decomposition is started at the same time and the user needs not do anything with the lenses un- til after 6 h when the process is ready. The currently used method with catalase for the decomposi¬ tion of hydrogen peroxide is carried out in such a way that catalase is added either as a solution or in the form of a tablet approximately, 20-30 minutes after the lenses have been placed in 3 % hydrogen .peroxide. The decomposition then starts immediately and goes very rapidly and completely. The advantages of this method are thus that the concentration of hydrogen peroxide is maintained during the desired period of time so that a safe disinfection is obtained. Furthermore the decomposition of the hydrogen peroxide is complete after the recommended time, which eliminates the risks of damages on the Seye. The disadvantage of the method is that the users consider the method more complicated to use than the method with platinum due to the fact that it requires two operations by the user at two different occasions. It follows herefrom that there is a need for a method for disinfecting contact lenses with a safety which can be com¬ pared with the catalase method and simple handling which is comparable with the platinum method. In prior patents (UK patent 2151039) it has been disclosed a method of making so called controlled release preparation in the form of a tablet of an inactivator for hydrogen peroxi¬ de. The described tablets give a release pattern of the inactivator which is rapid initially and slow at the end of the release period. This is unfavourable as the risk is then big that the concentration of hydrogen peroxide will decrea¬ se rapidly at the beginning, when high concentration is need¬ ed for killing the bacteria. Furthermore the concentration of the hydrogen peroxide will decrease more and more slowly and complete decomposition will occur after a long time and can even be jeopardized within the recommended period of ti¬ me. An ideal tablet preparation of a hydrogen peroxide inactiva- tor shall thus be able to give a slow decomposition at the beginning and a rapid decomposition after the disinfection is completed. The invention This invention is intended to fulfil the following requirements: - A disinfection-process (for contact lenses), which when initiated by the user does not require any further acti¬ on until the process is complete and the lenses are rea¬ dy for use. - A predetermined concentration of hydrogen peroxide shall be maintained during a specific period of time in order to secure a complete disinfection. When this point of time has been reached the decomposition rate shall be increased in order to secure that no hydrogen peroxide remains after the desired period of time (during the night). The invention comprises that tablet cores containing a cata¬ lytic substance such as catalase, is coated with a membrane, which consists of a water insoluble polymer which contains water soluble particles of a defined size and amount. The particles will be dissolved by the hydrogen peroxide solu¬ tion and a macroporous membrane is formed. Hydrogen peroxide penetrates through this membrane and a reaction starts bet- ween the hydrogen peroxide and catalase, whereby hydrogen pe¬ roxide decomposes for oxygen and water. The decomposition of the hydrogen peroxide is initially slow, but concurrently with the formation of more oxygen the membrane is expanded by the gas pressure and the penetration capacity of the mem¬ brane is increased, whereby catalase is released to the sur¬ rounding hydrogen peroxide solution and the reaction rate and the decomposition will increase. The polymer forming Jhe membrane should have good funifor¬ ming and adhesive properties and should be easily soluble in organic solvents, such as acetone and methylene chloride. Suitable polymers are derivatives of cellulose, acrylpoly- mers and vinylpolymers. Preferably the coating polymer is a polymer, which contains 80-95 per cent by weight of vinyl chloride, 1-19 per cent by weight vinylacetate and 0-10 per cent vinylalcohol. The coating should also preferably include a plastisizer. The amount of the p astisizer may vary between 30 and 150 per cent by weight of the polymer coating. Examples of suitable plastisizers are acetyltributylcitrate, polyethylene glycol , blown castor oil and glyceryltriacetate. The coating can al¬ so include sodium bicarbonate as a stabilizing agent. The poreforming substance, which is used according to tfie in¬ vention should be very water soluble, insoluble in the sol¬ vent, which is used for the coating, and toxicologically acceptable in the amounts used. Specifically perfered are sugars, such as sucrose and lactose and salts, such as sodium chloride. The particle size of the poreforming substance may vary bet¬ ween 0,1 and 100, preferably between 0,5 and 50 urn. The ra- tio between the amount of porecreating substance and coating polymer depends on the desired property. Usually this ratio should exceed 5 and preferably be between 10 and 30. According to a preferred embodiment of the invention the co¬ ating comprises a terpolymer of A w/w % 80-95 % vinyl chloride B w/w % 1-19 % vinyl acetate C w/w % 1-10 % vinyl alcohol and a plasticizer whereby the amount of plasticizer exceeds 30 per cent by weight of the terpolymer. Preferably the amount of plasticizer varies between 50 and 150 per cent by weight of the terpolymer. The ratio porecreating agent to terpolymer should preferably exceed 5. Most preferably this ratio should vary between 10 and 30. In this connection it should be specifically.pointed out that the coatings disclosed in the US patent 4,557,925 can not be used for the purpose of the present invention, as these coatings are not expandable and would therefore not give thte desired H2O2 decomposition profile. The coating thickness depends also on the desired property. It can vary between 5 and 300 μ , preferably between 10 and 200 μm. The coating procedure according to the invention can prefer¬ ably be carried out in the folowing manner: 1) A terpolymer containing (w/w%) 80-95 '/. VC (vinyl- chloride), 1-19 % VAC (vinylacetate), and 1-10 % V0H (vlnylalcohol) is dissolved in a solvent, e.g. acetone, methylenechloride, methylethylketone, or mixtures aceto¬ ne and ethanol , acetone and methylenechloride, or the like. 2) A suspension of the pore-creating substance is produced as fol ows: The pore-creating particles are ground either by dry milling in a ball mill or by wet-milling in a glass bead milling device to a defined particle size, preferably between 0,5 urn and 50 μm. The particles are dispersed in solvents or mixtures of solvents, such as those previ¬ ously mentioned, and mixed with the terpolymer solution. The ratio between pore-creating substance and terpolymer in the coating fluid is as previously described for the ratio in the coating. The coating fluid may, as previ¬ ously stated, include a plasticizer and sodium bicarbonate. The coating fluid, in the form of a suspension, is then applied on cores by conventional coating procedure. Examples of such coating procedures are pan coating, manual or spray-coating, Wϋrster coating, and other fluid-bed coating procedures. Coloring matter can also be incorporated in the coating fluid, and insoluble co¬ loring materials are preferred. ■ If a tablet containing catalase, which has been coated as above is placed in 10 ml hydrogen peroxide solution (3 %) sufficiently high concentration of hydrogen peroxide for di¬ sinfection of contact lenses and a complete decomposition of the hydrogen peroxide within 6 hours can be obtained, and this makes this method possible to use for disinfection over night. It 1s, however, also possible as is clearly demon¬ strated by Figure 2 that an essentially complete decomposi¬ tion can be obtained within two hours by using the composi¬ tion according to the Invention. It is believed that com- plete decomposition can be obtained within even shorter time if the coating is further modified. The following examples further illustrate the invention but should not be construed as limiting the invention. Example 1 Tablets including catalase (commercially available from Allergan) in a sufficient amount for decomposition of 10 ml hydrogen peroxide (3 %) were coated according to the proce¬ dure described above with a membrane consisting of 1 mg ter¬ polymer of vinylchloride, vinylacetate and vinylalcohol as a water insoluble membrane, 0,2 mg acetyltributylcitrate, 0,1 mg blown castor oil, 5,6 mg saccharose and 0,2 mg sodium bicarbonate. Acetone' as used as a solvent for the coating. 10 of these tablets were tested as follows in order to de¬ termine the effectiveness in destroying hydrogen peroxide. 10 ml of a 3 % (w/v) aqueous solution of hydrogen peroxide was held at room temperature. The tablet was introduced into the solution and periodic determinations of the H2O2 con¬ centration were made. The results of these determinations are summarized in Figure 1. Example 2 The catalase containing tablets from Allergan were coated by a coating fluid having the following composition: mg/tab]_et terpolymer (VC) m , (VAC) n , (V0H) 0 0,61 m=31, n=l, 0=2 saccharose 11,4 acetyl tributyl citrate 0,35 blown castor oil 0,26 sodium bicarbonate 0,39 acetone ad The coated tablets were tested to determine the effective¬ ness as in example 1 and the results are summarized in Figure 2.

Claims: C L A I M S 1. Composition including a core with a catalytic substance for decomposition of hydrogen peroxide to oxygen and wa¬ ter, characterized by that the core is surrounded by a membrane, which is expandable in aqueous medium and which comprises of a water insoluble polymer and a water soluble porecreating substance, which is randomly dist- ributed in the polymer, whereby the membrane permeabili¬ ty for the catalytic substance increases concurrently with the expansion of the membrane in the aqueous medium. 2. Composition according to claim 1, characterized that the polymer is a terpolymer of vinyl chloride, vinyl acetate and vinyl alcohol and the polymer coating also includes a plasticizer whereby the amount of plasticizer exceeds 30 per cent by weight of the terpolymer. 3. Composition according to claim 1 and 2, characterized by in that the amount of plasticizer varies between 50 and 150 per cent by weight of the terpolymer. 4. Composition according to preceeding claims, characteriz- ed in that the weight ratio porecreating agent to ter¬ polymer exceeds 5. 5. Composition according to any of the claims, characteriz¬ ed in that the weight ratio porecreating agent to terpolymer varies between 10 and 30. 6. Composition according to any of the claims 1-5, charac¬ terized by that it includes catalase as catalytic sub¬ stance. 7. Method for cleaning and disinfecting contact lenses, characterized by that the lenses together with a compo¬ sition according to claim 1-5 are suspended in an aqueous solution of H 2 0 2 , which during an initial period con- tains H 2 02 in an amount effective for cleaning and di¬ sinfection and after less than 8 hours, preferably less than 6 hours, includes less than 10 ppm H 2 0 2 . 8. Method according to claim 7 characterized in that the aqueous of H 2 02 'includes less than 10 ppm H 2 0 2 after less than 4 preferably less than 2 hours.

Inventors: BRANTVIK ANNIKA, FRANZEN CLAES, FRIGREN LENNART, PERSSON CHRISTIANE, WAXEGAARD STAFFAN, WENNGREN LENNART, BRANTVIK, ANNIKA, FRANZEN, CLAES, FRIGREN, LENNART, PERSSON, CHRISTIANE, WAXEGAARD, STAFFAN, WENNGREN, LENNART
Applicants: PHARMACIA AB
Application year: 1990
Main classification: C12N11
IPC codes: A61L2, A61L12, C12N11, G02C13