GB2088581A

GB2088581A - Papain and lactose containing tablet for cleaning contact lenses

Info

Publication number: GB2088581A
Application number: GB8129621A
Authority: GB
Original assignee: Smith and Nephew Associated Companies PLC
Current assignee: Smith and Nephew PLC
Priority date: 1980-10-02
Filing date: 1981-10-01
Publication date: 1982-06-09

Abstract

A water soluble tablet comprises 4 to 25mg. of papain and 30 to 260mg. of lactose for use in cleaning soft contact lenses. The tablet may contain 4 to 25mg ofa thiolic activating compound e.g. cysteine, 1 to 25mg of a chelating substance e.g. ethylenediaminetetra-acetic acid or salt thereof, or 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. 1419750 describes how an isotonic solution of protease enzymes may be employed to clean contact lenses and described a favoured tablet which, on dissolution in distilled water, can be used to prepare an isotonic solution of papain. German Offenlegungsschrift 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 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 30 to 260mg. of lactose or more suitably 50 to 250mg. of lactose.

The tablet of this invention may also contain a thiolic activating compound such as cysteine. 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 30 to 250mg. of lactose.

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

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 exampoe 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.

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.

Most aptly the tablet of this invention may contain 5 to 12 mg. of papain and preferably will contain 6 to 10 mg. of papain.

Most aptly the tablet of this invention will contain 60 to 120 mg. of lactose and preferably 75 to 100 mg. of lactose.

Most suitably the tablet of this invention will comprise 5 to 12 mg. of papain, 60 to 120 mg. of lactose, 5 to 15 mg. of ethylenediaminetetraacetic acid, 8 to 18 mg. of sodium or potassium bicarbonate or carbonate and 5 to 10 mgs. of sodium or potassium benzoate.

Preferred tablets of this invention will consist essentially of 6 to 10 mg. of papain, 75 to 100mg. of lactose, 5 to 1 Omg. of ethylenediaminetetraacetic acid, to long. 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 lOmg. of cysteine.

Most suitably in an alternative formulation the tablet of this invention will comprise 5 to 12 mg. of papain, 5 to 12mg. of cysteine, 35 to 120mg. of lactose, 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 alternative formulations of the tablets of this invention will consist essentially of 6 to 1 Omg. of papain, 6 to 1 Omg. of cysteine, 40 to 100mg. of lactose, 5 to 1 Omg. of ethylenediaminetetraacetic acid, 10 to 15mg. of sodium bicarbonate and Sto lOmg. of sodium benzoate.

The papain employed in this invention is suitably Prolase 300 (Trade Mark).

The lactose used in this invention is aptly a spray dried, rapidly dissolving form of lactose such as USP "Fast flo" lactose or its equivalents.

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 maybe included if desired, for example a polyoxyethylene-polyoxypropylene block copolymer such as Pluronic F68 (Trade Mark) or polyoxyethylene stearate such as Myrj 52 (Trade Mark). The tablets of this invention may be dissolved in distilled water to yield a cleansing solution suitable for soft contact lenses.

The tablets as hereinbefore 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 70mg. to 180mg.

will most aptly be dissolved in 10ml. 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 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 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 12 hours and preferably from 4to 8 hours. It is often convenient to clean the lens by keeping it at room temperature for this period that is at approximately 20"C. A shorter cleaning time may be envisaged if the temperature is maintained above 20"C but below the inactivation temperature of the enzyme, for example, the temperature may be advantageously maintained at 40"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 was prepared on a hand punch to give tablets of hardness 2.5kg.

(Monsanto tablet hardness tester).

Papain 7.5 mg Ethylenediaminetetraacetic Acid 6.5 mg Sodium bicarbonate 13 mg Sodium benzoate 8 mg Lactose 95 mg The tablet which was 5/16" in diameter 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 2 Atabletwas prepared as described in Example 1 except that in addition to the ingredients specified therein it also contain 4 mg. of Pluronic F68.

Example 3 A tablet of the following composition was prepared on a hand punch to give tablets of hardness 2.5kg.

(Monsanto tablet hardness tester).

Papain 7.5 mg.

L-cysteine (free base) 8.0 mg Ethylenediaminetetraacetic acid 6.5 mg Sodium bicarbonate 13.0 mg Sodium benzoate 8.0 mg Lactose 45.0 mg The tablet had a good appearance and dissolved quickly on shaking in 10ml. of distilled water to yield a solution capable of removing proteinaceous deposits from soft lenses.

Claims

1. A water soluble tablet which comprises 4 to 25 mg. of papain and 30 to 260 mg. of lactose.

2. A tablet as claimed in claim 1 which comprises 4to 25 mg. of papain and 50 to 250 mg. of lactose.

3. A tablet as claimed in claim 2 which also includes 1 to 25 mg. 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 or claims 3 or 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 20 mg. of a tabletting acid.

8. A tablet which comprises 4 to 25 mg. of papain, 4 to 25 mg. of a thiolic activating compound and 30 to 250 mg. of lactose.

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 25 mg. 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.

12. A tablet as claimed in either of claims 10 or 11 in which the chelating substance is ethylenediaminetetraacetic acid.

13. A tablet as claimed in any of claims 8 to 11 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.

13. A tablet as claimed in any of claims 8 to 13 which also contains from 2 to 20 mg. of a tabletting aid.

14. 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 13 for sufficient time to clean the lens.

15. A method as claimed in claim 14 in which the contact lens is a soft contact lens.