GB2117534A - Papain containing tablet for cleaning contact lenses - Google Patents

Abstract

A water soluble tablet comprises 4 to 25mg of papain and 15 to 50mg of potassium chloride as tablet diluent, for use in cleaning soft contact lenses. The tablet may contain 4 to 25mg of a thiolic activating compound e.g. cysteine, 1 to 25mg of a chelating substance e.g. ethylenediaminetetraacetic acid or salt thereof, and sodium or potassium bicarbonate or carbonate to render the pH of an aqueous solution of the tablet 4 to 9.

Description

SPECIFICATION Soluble tablet and use thereof The present invention relates to a soluble tablet containing papain and to the use of said tablet in forming a solution which may be employed in removing proteinaceous deposits from contact lenses.

Papain has long been known to be suitable for removing proteinaceous deposits from articles that come into contact with humans. One class of articles that require to be treated to remove proteinaceous deposits is contact lenses. British Patent No. 141 9750 describes how an isotonic solution of protease enzymes may be employed to clean contact lenses and describes a favoured tablet which, in dissolution in distilled water, can be used to prepare an isotonic solution of papain. German Offenlegungschrift P2854278 describes how non-ionic wetting agents may be used to enhance the effectiveness of isotonic solutions of proteases.It has been generally believed that in order to treat soft (hydrophilic) contact lenses the enzyme solution employed should be isotonic and to this end tablets such as "Hydrocare" (Trade Mark of Allergan Pharmaceuticals) contain sufficient sodium chloride to render the cleaning solution isotonic.

Unfortunately known tablets have tended to be somewhat slow to dissolve and it would be a considerable advantage if a more rapidly dissolving tablet could be found.

It has now been discovered that a tablet can be prepared that dissolves to yield a solution capable of removing proteinaceous deposits from soft contact lenses. The new tablet does not dissolve to produce an isotonic solution but that is not now deemed to be necessary despite the numerous indications in the prior art that cleaning solutions should be isotonic.

The present invention provides a tablet which comprises 4 to 25mg of papain and 1 5 to 260mg of a tablet diluent.

By tablet diluent is meant an inert substance which is added to the active ingredient to increase the bulk in order to make the tablet a practicai size for compression. Our copending British Application No. 8129621, now published as UK Patent Application GB 2088581A discloses a tablet comprising papain and lactose. Excellent and effective though the tablets described therein are it has now been found that by replacing a substantial part of or all of the lactose by an ionic compound as tablet diluent, tablets having an improved ease of manufacture, better binding properties, better colour stability on storage and an improved rate of dissolution may be prepared. Suitable diluents which generate ions when dissolved in water include the sodium and potassium salts of hydrochloric or hydrobromic acid. Preferred ionic diluents are sodium and potassium chlorides.A particularly preferred ionic diluent is potassium chloride.

Most aptly the tablet will contain no lactose.

When the diluent is an ionic compound the tablet will contain from 1 5 to 50mg of the diluent and preferably 20 to 40mg of the ionic diluent in each tablet. Such tablets when dissolved in 10ml of water will yield a solution which is not isotonic.

From the foregoing it is clear that the present invention comprises a water soluble tablet which comprises 4 to 25mg of papain and 1 5 to 50mg of potassium chloride.

The tablet of this invention may also contain a thiolic activating such as cystiene. Thus in an alternative formulation the present invention provides a tablet which comprises 4 to 25mg of papain, 4 to 25mg of a thiolic activating compound and 1 5 to 50mg of potassium chloride as tablet diluent.

Suitable thiolic activating compounds include cysteine and acid addition salts thereof, sodium bisulphite, sodium metabisulphite and dithiothreitol. Most aptly the thiolic activating compound is cysteine.

Suitable tablet diluents are hereinbefore described.

It has however, proved desirable to include within the tablet a substance capable of chelating multivalent ions such as calcium. The agent of choice for this purpose is ethylenediaminetetraacetic acid. This compound may be employed as the acid or as a sodium or potassium salt such as disodium ethylenediaminetetraacetic acid or the like. However it has been found that significant advantages in ease of tablet formation occur if the parent ethylenediaminetetraacetic acid is employed. This is a departure from the conventional method of using the compound as the disodium salt.

Normally the tablet of this invention will contain from 1 to 25mg of ethylenediaminetetraacetic acid or a sodium or potassium salt thereof which, as said hereinbefore it is preferred to employ the parent acid.

The tablet of this invention will also aptly contain a sodium or potassium bicarbonate or carbonate to render the pH of the cleansing solution acceptable, for example from 4 to 9 and more suitably from 5 to 8. In general this requires that the tablet of this invention contains from 1 to 25mgs of sodium or potassium bicarbonate or carbonate. Use of bicarbonate or carbonates for this purpose is advantageous as it can lead to more rapid dissolution of the tablet due to small amounts of effervescence. However the combination of the components of the tablet does not have buffering capacity when dissolved in water.

If desired the tablet of this invention may contain small amounts of tabletting aids, for example sodium or potassium benzoate. Most aptly such aids are present in the range of 2 to 20mgs per tablet.

If desired the tablet of this invention may also contain a tablet lubricant in the form of a water soluble polymer. Suitable polymers include the water soluble polyalkylene glycols, preferably a polyethylene glycol. Suitable polyethylene glycols are those known as Carbowaxes (Registered trade mark of Union Carbide Co.) having a molecular weight of approximately 4,000 to 8,000.

A preferred polyethylene glycol is one having a molecular weight of 8,000, known as Carbowax PEG 8000. Suitably the tablet will contain from 1 to 1 Omg and preferably 2 to 5mg of the tablet lubricant.

Most aptly the tablet of this invention may contain 5 to 12mg of papain.

Most suitably the tablet of this invention will comprise 5 to 12mg of papain, 1 5 to 50mg of potassium chloride, 5 to 15mg of ethylenediaminetetraacetic acid, 8 to 18mg of sodium or potassium bicarbonate or carbonate and 5 to 1 Omg of sodium or potassium benzoate.

Preferred tablets of this invention will consist essentially of 6 to 20mg of papain, 20 to 35mg potassium chloride, 5 to 1 Omg of ethylenediaminetetraacetic acid, 1 to 15mg of sodium bicarbonate and 5 to 1 Omg of sodium benzoate.

Most aptly the tablet of this invention may also contain 5 to 12mg of cysteine and preferably will contain 6 to 1 Omg of cysteine.

Most suitably in an alternative formulation the tablet of this invention will comprise 5 to 12mg of papain, 5 to 12mg cysteine, 1 5 to 50mg of a tablet diluent, 5 to 25mg of ethylenediaminetetraacetic acid, 8 to 18mg of sodium or potassium bicarbonate or carbonate and 5 to 1 Omg of sodium or potassium benzoate.

Preferred alternative formulations of the tablets of this invention will consist essentially of 6 to 20mg of papain, 6 to 1 Omg of cysteine, 20 to 35mg of potassium chloride, 5 to 1 Omg of ethylenediaminetetraacetic acid, 10 to 15mg of sodium bicarbonate and 5 to 1 Omg of sodium benzoate.

A particularly preferred alternative formulation will comprise 6 to 20mg of papain, 6 to 1 Omg of L-cysteine, 20 to 35mg of potassium chloride, 5 to 20mg of ethylenediaminetetraacetic acid, 5 to 1 Omg of sodium carbonate and 2 to 5mg of polyethylene glycol (molecular weight 4000).

The papain employed in this invention is suitably Prolase 300 (trade mark).

If desired other small amounts of conventional excipients may be included with the tablet formulation. Thus for example small amounts of sodium chloride (for example 2-5%) may be employed as long as it does not substantially effect the rate of dissolution of the tablet. Similarly a wetting agent which is aptly a solid non-ionic surface active agent may be included if desired, for example a polyoxyethylene-polyoxypropylene block copolymer such as Pluronic F68 (trade mark). or polyoxyethylene stearate such as Myrj 53 (trade mark). The tablets of this invention may be dissolved in distilled water to yield a cleansing solution suitable for soft contact lenses.

The tablet as herein before described will in use be dissolved in water, preferably distilled water, to give a solution which is significantly less than isotonic. In general tablets having a weight of from 50mg to 180mg will most aptly be dissolved in 1 Oml or other similar volume of water to give a solution which is significantly less than isotonic and is suitable for removing proteinaceous deposits.

In an important aspect, this invention provides a method of removing proteinaceous deposits from a contact lens which method comprises contacting the said lens with an aqueous solution, formed by dissolving in water a tablet of this invention for sufficient time to clean the lens.

Suitably one tablet may be used per lens. In general the tablet will be dissolved in 1 Oml of distilled water. In use the solution will be made up in a suitable container, for example a glass bottle closed by a plastic cap. The lens may be placed in the solution and the container closed.

Alternatively the lenses may be placed in a perforated lens holder so that the lenses from the right and left eye are readily identified and the lens holder placed in a solution prepared from a tablet and distilled water such that both lenses are covered by the enzyme solution.

In general the lens will be in contact with the solution of the enzyme for from 1 to 24 hours, suitably from 2 to 1 2 hours and preferably from 4 to 8 hours. It is often convenient to clean the lens by keeping it at room temperature for this period, that is approximately 20deg.C. A shorter cleaning time may be envisaged if the temperature is maintained above 20 deg.C. but below the inactivation temperature of the enzyme, for example, the temperature may be advantageously maintained at 40deg.C.

After cleaning the lens will be rinsed with distilled water and sterilised before re-insertion in the eye in a conventional manner.

The following Examples illustrate the invention: Example 1 A tablet of the following composition is prepared on a hand punch to give tablets of a hardness 3.5kg.

(Monsanto tablet hardness tester).

Papain 7.5mg Ethylenediaminetetraacetic acid 6.5mug Sodium bicarbonate 13.0mug Sodium benzoate 5.0mg Potassium chloride 25.0mg The tablet which is 3/16" in diameter has a good appearance and dissolved quickly on shaking in 10ml of distilled water to yield a solution capable of removing proteinaceous deposits from soft contact lenses.

Example 2 A tablet of the following composition was prepared on a hand punch to give tablets of hardness 3.5kg (Monsanto hardness tester).

Papain 7.5mg L-cysteine (free base) 8. Omg Ethylenediaminetetraacetic acid 8.Omg Sodium carbonate 5.0mg Potassium chloride 30.0mg Polyethylene glycol (M.W. 4000) 3.0mg The tablet had a good appearance and dissolved quickly on shaking in 1 Oml of distilled water to yield a solution capable of removing proteinaceous deposits from soft lenses.

Example 3 A tablet of the following composition was prepared in a hand punch to give tablets of hardness 3.5kg (Monsanto hardness tester).

Papain 7.5mg L-cysteine (free base) 8.0mg Sodium bicarbonate 20.0mg Sodium benzoate 5.0mg Ethylenediaminetetraacetic acid 8.0mg Sodium chloride 20.0mg The tablet had a good appearance and dissolved on shaking in 1 Oml of distilled water to yield a solution capable of removing proteinaceous deposits from soft lenses.

Example 4 A tablet of the following composition is prepared on a hand punch to give tablets of hardness 3.5kg (Monsanto hardness tester).

Papain 7.5mg L-cysteine (free base) 8.0mg Ethylenediaminetetraacetic acid 8.Omg Sodium carbonate 5.0mg Potassium chloride 30.0mg Polyethylene glycol (M.W. 6000) 3.0mg The tablet has a good appearance and will dissolve quickly on shaking in 1 Oml of distilled water to yield a solution capable of removing proteinaceous deposits from soft lenses.

Example 5 A tablet of the following composition was prepared in a hand punch to give tablets of a hardness 3.5kg (Monsanto hardness tablet tester).

Papain 13.5mg L-cysteine (free base) 8.0mg Ethylenediaminetetraacetic acid 8.Omg Sodium carbonate 5.0mg Potassium chloride 30.0mg Polyethylene glycol (M.W. 6000) 3.0mg The tablet has a good appearance and will dissolve quickly on shaking in 1 Oml of distilled water to yield a solution capable of removing proteinaceous deposits from soft lenses. The resultant solution is not isotonic.

Claims (14)

1. A water soluble tablet which comprises 4 to 25mg of papain and 5 to 50mg of potassium chloride.

2. A tablet as claimed in claim 1 which comprises 4 to 25mg of papain and 20 to 40mg of potassium chloride.

3. A tablet as claimed in claim 2 which also includes 1 to 25mg of a substance capable of chelating multivalent ions.

4. A tablet as claimed in claim 3 in which the chelating substance is ethylenediaminetetraacetic acid or a sodium or potassium salt thereof.

5. A tablet as claimed in either of claims 3 to 4 in which the chelating substance is ethylenediaminetetraacetic acid.

6. A tablet as claimed in any of claims 2 to 5 which also contains sodium or potassium bicarbonate or carbonate sufficient to render the pH of an aqueous solution of the tablet from 4 to 9.

7. A tablet as claimed in any of claims 2 to 6 which also contains 1 to 20mg of a tabletting aid.

8. A water soluble tablet which comprises 4 to 25mg of papain, 4 to 25mg of a thiolic activating compound and 1 5 to 50mg of potassium chloride.

9. A tablet as claimed in claim 8 in which the thiolic activating compound is cysteine.

10. A tablet as claimed in either of claims 8 or 9 which also contains 1 to 25mg of a substance capable of chelating multivalent ions.

11. A tablet as claimed in claim 10 in which the chelating substance is ethylenediaminetetraacetic acid or a sodium or potassium salt thereof.

1 2. A tablet as claimed in either of claims 10 or 11 in which the chelating substance is ethylenediam i netetraacetic acid.

1 3. A tablet as claimed in any of claims 8 to 1 2 which also contains sodium or potassium bicarbonate or carbonate sufficient to render the pH of an aqueous solution of the tablet from 4 to 9.

14. A tablet as claimed in any of claims 8 to 1 3 which also contains from 1 to 20mg of a tabletting aid.

1 5. A method for removing proteinaceous deposits from a contact lens which method comprises contacting said lens with an aqueous solution formed by dissolving in water a tablet as claimed in any of claims 1 to 14 for sufficient time to clean the lens.

1 6. A method as claimed in claim 1 5 in which the contact lens is a soft contact lens.